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Bulletin

2017www.csmb-scbm.ca

The Canadian Society for Molecular BiosciencesLa Société Canadienne pour les Biosciences Moléculaires

CSMB | SCBM Bulletin 2017 1

Bulletin

2017www.csmb-scbm.ca

The Canadian Society for Molecular BiosciencesLa Société Canadienne pour les Biosciences Moléculaires

2 CSMB | SCBM Bulletin 2017

Table of Contents

CSMB Board for 2017 ......................................................................................................................................4President’s Report 2017 ..................................................................................................................................6Incoming Members of the Executive Board ...................................................................................................9 Paola Marignani, Councillor .................................................................................................................9 NafisaJadavji,Councillor,TraineeRepresentative.............................................................................10 BensunFong,Councillor,TraineeRepresentative..............................................................................10Minutes of the 60th Annual General Meeting 2017 ....................................................................................11Financial Statement 2017 .............................................................................................................................1460th Annual Meeting, Ottawa, Ontario ........................................................................................................19 MeetingReport:“CelebratingCanadianMolecularBiosciences: ......................................................19 fromOrganellestoSystemsBiology ScenesfromtheMeeting...................................................................................................................22Trainee Committee Activities 2017 ...............................................................................................................302018 CSMB Award Designates ......................................................................................................................31 CSMBNewInvestigatorAward:KateyRayner...................................................................................31 CanadianSciencePublishingSeniorInvestigatorAward:RichardRachubinski.................................32 ArthurWynneGoldMedalAward:MonaNemerandJimWoodgett................................................33Award Articles 2017 ......................................................................................................................................35 Canadian Science Publishing Senior Investigator Award: Sergio Grinstein .....................................35 “Receptors and integrins interact with the cytoskeleton and the exoskeleton toinitiatephagocytosis” CSMB New Investigator Award: Martin Schmeing ...........................................................................40 “Structuralinsightintononribosomalpeptidesynthetases, naturalantibioticfactories” News from Member Departments ...............................................................................................................48 Dalhousie University .........................................................................................................................48 Hospital for Sick Children Research Institute ...................................................................................49 McGill University...............................................................................................................................50 McMaster University.........................................................................................................................52 Princess Margaret Cancer Centre ......................................................................................................54 Ryerson University ............................................................................................................................56 Simon Fraser University ....................................................................................................................57 Sunnybrook Research Institute .........................................................................................................57 Université de Sherbrooke .................................................................................................................59


University of Alberta ........................................................................................................................ 59 Biochemistry ......................................................................................................................... 59 Physiology ............................................................................................................................. 61

University of Calgary .........................................................................................................................62 Biochemistry and Molecular Biology .....................................................................................62 Biological Sciences .................................................................................................................63

University of Guelph .........................................................................................................................65University of Lethbridge ....................................................................................................................68University of Manitoba .....................................................................................................................70University of Toronto ........................................................................................................................71

Biochemistry ..........................................................................................................................71Cell and Systems Biology .......................................................................................................78

Molecular Genetics ................................................................................................................79University of Toronto Mississauga ....................................................................................................83

CSMB-Sponsored Events ...............................................................................................................................86


CSMB Board for 2017President/PrésidentDr.PhilipHieterUniversityofBritishColumbiaMichaelSmithLaboratories2185EastMallVancouver,BCV6T1Z4Tel:(604)822-5115Email:[email protected]

Past-President/Président Précédent and Chair, Nominating Committee/Président, Comité de mise en candidatureDr.KristinBaetzUniversityofOttawaDepartmentofBiochemistry,Microbiology&Immunology451SmythRoad,RogerGuidonHallOttawaONK1H8M5Tel:(613)562-5800X8592E-mail:[email protected]

Vice-President/Vice-PrésidentDr.TarikMöröyInstitutderecherchescliniquesdeMontrealIRCMLaboratoryonHematopoiesisandCancer110AvenuedesPinsOuestMontreal,QCH2W1R7Tel:(514)987-5501E-mail:[email protected]

Treasurer/TrésorierDr.JanRaineyDalhousieUniversityDepartmentofBiochemistryandMolecularBiologyTupperMedicalBuildingHalifaxNSB3H1X5Tel:(902)494-4632E-mail:[email protected]

Secretary/SecrétaireDr.JamesDavieUniversityofManitobaChildren’sHospitalResearchInstituteofManitoba600A-715McDermotAvenue,JohnBuhlerResearchCentreWinnipeg,MBR3E3P4Tel:(204)975-7732Email:[email protected]

Councillor/ConseillerDr.ChristianBaronUniversitédeMontréalDépartementdebiochimieC.P.6128,Succ.Centre-villeMontréal,QCH3C3J7Tel:(514)343-6372E-mail:[email protected]

Councillor/ConseillerDr.BarbaraKartenDalhousieUniversityDepartmentofChemistryandMolecularBiologySirCharlesTupperMedicalBuilding9G5850CollegeStreet,POBox15000Halifax,NSB3H4R2Tel:(902)494-2332Email:[email protected]

Councillor/ConseillerDr. Paola MarignaniDalhousieUniversityDepartmentofBiochemistryandMolecularBiologySirCharlesTupperMedicalBuilding9G,5850CollegeStreet,POBox15000Halifax,NSB3H4R2Tel:(902)292-4307Email:[email protected]


Councillor/ConseillerDr.JustinNodwellUniversityofTorontoDepartmentofBiochemistry1King’sCollegeCircleToronto,ONM5S1A8Tel:(416)978-2696E-mail:[email protected]

Councillor/ConseillerDr.MichelleScottUniversitédeSherbrookeDepartmentofBiochemistry3201JeanMignaultSherbrooke,QCJ1E4K8Tel:(819)821-8000x72123Email:[email protected]

Councillor/ConseillerDr.Hans-JoachimWiedenUniversityofLethbridgeDepartmentofChemistryandBiochemistry4401UniversityDriveWLethbridge,ABT1K3M4Tel:(403)329-2303Email:[email protected]

Councillor/ConseillerTrainee Representative/Représentante des stagiairesMr.BensunC.FongUniversityofOttawaDepartmentofCellularandMolecularMedicine451SmythRoadOttawa,ONK1H8M5Tel:(613)404-9104E-mail:[email protected]

Councillor/ConseillerTrainee Representative/Représentante des stagiairesDr.NafisaM.JadavjiCarletonUniversityDepartmentofNeuroscience1125ColonelByDriveSocialSciencesBuildingOttawa,ONK1S5B6Tel:(613)562-5800x8135E-mail:[email protected]

Bulletin Editor/Éditeur du BulletinDr.FrancesSharomUniversityofGuelphDepartmentofMolecularandCellularBiologyScienceComplexRm.4446Guelph,ONN1G2W1E-mail:[email protected]


President’s Report 2017 Dr. Phil Hieter

In2017,CSMBrampedupefforts,fromthemomentumbuiltinpreviousyearsundertheleadershipofformerPresidentsKristinBaetzandChristianBaron,toadvocateforincreasedfundingoffundamentaldiscoveryresearchbythefederalgovernment. Indeed,2017wasapivotalyear forscienceadvocacyforseveralreasons.First,theCanadianscientificcommunity had experienced a serious decline in federalsupport for science research and teaching over the pastdecade.Second,wewereencouragedbythereleaseoftheFundamentalScienceReviewReport(the“NaylorReport”)that was commissioned by Dr. Duncan, the Minister ofScience.ThisreportoutlinesatrulyoutstandingvisionforCanadian research and a roadmap for increased fundingand better tri-council organization that would restoreCanada to its rightful place among the global leaders inresearchanddevelopment.

Theimpactoffundamentalresearchfundingonthenationalgoodisdifficulttooverstate,andshouldbean importantconcernforourmembersofparliamentandthepublicatlarge.Basicresearchprovidestheknowledgebasewithoutwhich innovation and technological development couldnot take place. We train highly qualified personnel whorepresent the country’s future.We support solidmiddle-class jobs in conducting research with federal support.Cutting-edge research is a beacon for highly qualifiedimmigrants.

Starvingbasicresearchisacapitalstrategicerror,butthatiswhatoccurredover a 10-yearperiod (2007-2016). TheFundamental Science Review provides a well-designedactionplantostrengthenresearchandtraininginCanadaand its impact on the economy. Researchers recognizetheacutebudgetarypressuresourgovernmentfaces,andthe fiscal responsibility required tomanage an advancedeconomy in uncertain times. However, advancing healthcare, industry,andeconomicwell-beingareconstantpre-occupations of Canadians, and as basic researchers, weareimportantcontributorstoadvancingallthreeofthese.

CSMBwillcontinuetoworktogetherwithyoutomaketheargumentsforfundamentalresearchsothatthegovernmentwillhavethevisiontorobustlyfundbasicresearchinordertoensurethefuturesuccessandwell-beingofCanada.

Below,IhighlightsomeoftheinitiativesandeventsthattheCSMBhaspoureditseffortsintoin2017.

Trainee activitiesIn support of the Naylor report, the trainee committeelaunchedasuccessfulTwittercampaign in thesummerof2017titled“PutafaceonCanadianScience”.ThefocuswastoadvocateforthefederalgovernmenttoincreasefundingforbasicscienceinCanada.Forthecampaign,traineeswereaskedtodescribetheirresearch,takeapictureofthemselvesdoingresearch,andpostitonTwitter.TweetsweresenttoJustin Trudeau andBillMorneau. Thehashtags thatwereusedwere: #NextGenCanScienceand#SupportTheReport.Approximately 150 trainees across Canada participated inthecampaign.Thetraineecommitteealsoprovidedfeedbackfor the career skillsworkshop offered at the 61st AnnualMeetingoftheCanadianSocietyforMolecularBiosciences.Alistofgraduatestudentassociations(GSA),post-doctoralassociations, undergraduate associations and professionaltrainee societies/associationsacrossCanada,wasalsoputtogether by the committee. In addition, CSMB supportedseveralstudent-ledsymposiaandresearchconferenceswith$500awards,asdescribedlaterinthisBulletin.

CSMB Board response to Budget 2017The CSMB Board issued a statement of concern thatBudget 2017 (released in February 2017) fell short insupport of discovery research. CSMB expressed surpriseand disappointment that besides somemodest targetedinvestmentsintoprogramssuchastheStemCellnetwork,thebudgetdidnotcontainanynewresourcesfordiscoveryresearch, especially for the open competitions at theCanadianInstitutesofHealthResearch(CIHR)andtheNaturalSciencesandEngineeringResearchCouncil(NSERC).CSMB

CSMBPresident,PhilHieter


questionedtherationaleforexpandingbothinfrastructureandnumbersofresearchersinacontextwherefundingforCIHR andNSERC is stagnant. Theoperational funding forfundamentalresearch inCanadahaddeclinedwellbelowournation’sresearchcapacity,andasaconsequence,manyCanadianresearchlabsweredownsizingorclosing,therebyeliminatingskilledjobsandsquanderingpriorinvestmentsin research. CSMB strongly supported the allocation ofresourcesforcreatingtheofficeofaChiefScienceAdvisorbutwasconcernedthattherecommendationsofthelonganticipated Fundamental Science Review had not beenreleased. CSMB also supported measures to improveskillstraining,toadvancegenderequity,toattractforeigntalentandtosupporttheNationalResearchCouncil.CSMBpledgedtoworkcloselywiththeChiefScienceAdvisorandwith the Ministers of Science and Health to implementthe anticipated Science Review’s recommendations tostrengthenCanada’sresearchenvironment.

March for ScienceOnApril22,2017,theMarchforScience,whichcoincidedwithEarthDay,tookplaceinmorethan500citiesaroundthe world, with 18 marches occurring in cities acrossCanada.Collectively, themarcheswereahugesuccess inraisingawarenessoftheimportanceofscienceresearch.InOttawa,over700peopleattendedtheMarchforScience.Theoverarchingmessage fromall the speakerswas howcritical science and evidence-based decisionmaking is toCanada.ThenCSMBPresidentKristinBaetzspokeattherallyonParliamentHillwithastrongmessagethatsocietyneedsscienceifwearetotackleproblemssuchasclimatechange,thenextsuperbug,foodsecurity,anagingpopulationandfutureproblemsthatwecannotyetimagine.Hermessagewasthatthroughscience,Canadawillimprovethelivesofitscitizensandcontributetothewell-beingoftheworld.ShealsointroducedtherecommendationsoftheFundamentalScienceReview (thathad justbeen releasedonApril 10)andmadeacalltoarmsforitsgeneralsupport.

60th CSMB Annual ConferenceThe60thannualCSMBconference,“CelebratingCanadianMolecular Biosciences- from Organelles to SystemsBiology”was held inOttawa onMay 16-20, 2017. By allaccounts thiswasanoutstandingmeeting- ithadall thenecessaryingredientsofgreatpeople,greatprogram,greatvenue,andflawlesslogistics,tocreateanatmospherethatgeneratedgreatscience,lotsofinteraction,discussionandexchangeofideas,newtechnology,newcollaborations,andfun.Therewere415registeredparticipants,81talks(with

morethan60%selectedfromabstracts),and234posters.AfullmeetingreportisfoundinthisBulletin.

CSMB calls on its members to #Support the Report through interactions with Members of ParliamentCSMBmembers at all career stageswere encouraged toengage their localMPs to introduce themselves,describetheir work and why it is important, to articulate howdecreasesinfundamentalresearchfundinghaveimpactedthemdirectly,tointroducetheNaylorReport,andtovoicesupport for its full implementation.Throughourwebsite,CSMBassistedbyprovidingsuggestions, instructions,andinformationtofacilitatetheseinteractions.Oneavenuewastowrite a personal letter to their MP, andtoincludePrimeMinisterJustinTrudeau,MinisterofFinanceBillMorneau,MinisterofScienceKirstyDuncan,MinisterofHealthJanePhilpottandMinisterofInnovation,ScienceandEconomicDevelopmentNavdeepBains.Our colleagues at EvidenceforDemocracyhadalsodevelopedagreattoolkittoaidinletterwriting.AsecondavenuewastorequestameetingwiththeirMP. TheideawastomeetoverthesummerwhiletheMPsareback in their ridings and considerofferingatouroftheirlab.Memberswerealsoencouragedtomakethese meetings known by tweeting using the hashtag:#SupportTheReport.Forexample,atmyinstitutionduringthe summer of 2017, a total of 17MPs and 12 CabinetMinisters visited the UBC campus to meet with variousfacultymembersanduniversityleaderstodiscusstheneedfor increased federal funding of fundamental researchthrough the tri-councils. Similar events occurred acrossCanada.

CSMB submits pre-budget consultation to the House of CommonsOn August 4, 2017, the CSMB Advocacy committeesubmitted a pre-budget consultation to the House ofCommonsStandingCommitteeonFinance.Thedocumentarticulated the urgent need to restore investment infundamentalresearch,inordertogeneratetheknowledgethat fuels innovationandtotrain thenextgenerationforjobs in an increasingly knowledge-driven economy. Inparticular,theessentialcomponentofoperatinggrantsthatfueltheday-to-dayexpensesofresearchandpaypersonnel(students,post-docs,technicians)isinadequate.TheCSMB,therefore,stronglyurgedthefederalgovernmenttorestorediscoveryresearchandtrainingwithsignificantinvestmentsintotheopencompetitionsatCIHR,NSERC,andSSHRCinthe2018andfuturebudgets.Specifically,theCSMBstronglyendorsed the recommendations of the Naylor Report


for 1) Increased investmentof $485Mover four years tosupportinvestigator-initiatedfundamentalresearch(CIHR,NSERC, SSHRC), 2) Increased investment in scholarshipand fellowship programs to an additional $140M overfouryearstosupporttrainees,3)Stablefunding,stagedinoverfouryears,fortheCanadaFoundationforInnovation(CFI)at$300Mperyeartosupportresearchinfrastructure,and 4) Increased investment of $485M in facilities andcdministrationcoststohostinstitutionsoverfouryearstosupportinstitutionalcostsofresearch.

CSMB Board members travel to Ottawa in support of the Fundamental Science ReviewSeveralCSMBBoardmembersmetwithvariousMPsandMinisters at theirOttawaoffices to voice supportof theFundamental Science Review. For example, in my case,I travelled to Ottawa as part of a delegation led by theUBCOffice of Government Relations and UBC PresidentProfessor Santa Ono. Dr. Liisa Galea, a professor andresearcherattheUBC’sCentreforBrainHealth,alsojoinedthe delegation.Over two days, our groupmetwith twoCabinetMinisters,includingCanadianMinisterofScienceHon. Kirsty Duncan, Deputy Minister of Health CanadaSimonKennedy,twoDeputyDirectors,threeParliamentarySecretaries,twoChairsofStandingCommittees,theChairoftheLiberalCaucus,andthePresidentofUniversitiesCanadaPaulDavidson.Themeetingswereusedtoemphasizetheimportanceofbasic scienceandtoadvocate forsupportfrom MPs for the implementation of the FundamentalScienceReviewrecommendations.

New Board committee structure and appointment of At-Large membersAnewandexpandedCSMBcommitteestructure,mandatedand developed by the Board of Directors at theirMarch2017Boardmeeting,waslaunchedinSeptember2017.TheCommitteesthatwereestablishedare:Executive,Advocacyand Communication, Membership and Diversity, Financeand Development, Awards, Nominations, and Trainees.In addition to Boardmembers, each committee includesseveral“At-Large”members,chosenfromtheactiveCSMBmembershipfollowinganapplicationprocess.Acompletelist of the individual committee mandates and currentmemberscanbefoundontheCSMBwebsite.FollowingageneralcallforapplicationsinSeptember,thefirstroundof“At-Large” committeememberpositionswerechosen foreachofthecommitteesoftheCSMBBoard.TheAt-LargemembersthatwereselectedwereJulieClaycombandJimWoodgett (Advocacy and Communication), Peter Stirling(Membership and Diversity), Imogen Coe (Finance and

Development), Esther Verheyen (Awards), Sarah Hughes(Conferences),BillStanford(Nominations),SenthillKumar,ErinKennedyandMacKenzie Lawrence (Trainee).TheAt-Large members will have two-year terms, and anotherroundwill be added in July 2018 such that oneAt-Largecommitteememberwillbecycledon,andoneoff,onanannualbasisinsubsequentyears.

Campaign to encourage business leaders to advocate for the Fundamental Science Review to governmentInNovember2017,theCSMBBoardlaunchedacampaigntoencouragebusinessleaderstosubmitletterstotheFederalFinanceCommitteeinsupportoftheNaylorReportfundingrecommendationsthroughasecondpre-budgetconsultationprocessthatopenedinNovember2017(#YourBudget2018).MembersoftheCSMBBoardsetupface-to-facemeetingswith localbusiness/biotech leadersacrossCanadatobriefthemontheNaylorReportcontent,andtoraiseawarenessthatCanadawasinafundingcrisis.Industryreliesnotonlyonfoundationaldiscoveries,butalsoabsolutelyonthepoolofuniversitysciencegraduatestoprovideaskilledworkforceintheircompanies.Whenmadeawareofthefundingdecline(35%perresearcherforinvestigator-initiatedresearchsince2007),andtheinternationalcomparisons(%GDPbudgetedtoRandDrelativetoothercountries),manyindustryleadersdecidedtosubmitstatementsrecommendingthatCanadare-invest in investigator-initiated fundamental researchthroughthetri-councils(CIHR,NSERC,SSHRC),atthelevelsrecommendedintheNaylorReport.Atemplateletterwasputtogether(incollaborationwithEvidenceforDemocracy)toassistbusinessleadersincomposingasupportletter,andinformationwas provided for submitting it easily throughtheappropriatechannels.

Looking forwardThe CSMB represents thousands of academic researchfaculty,fellows,andstudentsinthemolecularbiosciencesacross Canada.Ourmandate is to advance and promotemolecular biosciences, with a focus on advocating forrobustandsustainablefundingforfundamentalresearchinCanada. IhaveenjoyedservingasPresidentoftheCSMBandamgratefulforthehardworkandeffortsoftheCSMBBoardandothermembersofthescientificcommunity.Weknowthereismuchmorethatweneedtodotofullyrealizethe tremendous potential of Canadian research, and weneedyourcontinuedsupport.Welookforwardtocontinuetoworktogetherwithyou,andwithgovernmentofficialsandall partners and stakeholders to strengthenCanada’sresearchenvironmentintheyearsahead.


Incoming Members of the CSMB Executive Board

Dr. Paola Marignani, CouncillorDr.Marignanistartedherscientificcareerat theearlyageof6,wheresheshowedanaptitudeforSTEM.Dr.Marignani’sformaleducationstartedwitha B.Sc. Hons. (University of Windsor) in biology and chemistry, followedby M.Sc. studies (University of Western Ontario) in neuropathology andneurodegenerativediseases,andaPh.D.(McMaster)inlipidsandmembranebiophysics.Dr.Marignaniexpandedher scientificportfoliobypursuing theearlydaysofsignaltransductionasapost-doctoralfellowatHarvardUniversity,whereshecreatednewgeneexpressionstrategiesforunderstandingsignallingoftumoursuppressor/oncogenes.AfterherreturntoCanada,Dr.Marignani’sfellowshipfocussedonmassspectrometryattheSamuelLunenfeldResearchInstitute and cancer biology at the Ontario Cancer Institute. In 2013, Dr.Marignani successfully completeda rigorousExecutiveMBAprogram fromthe Ivey School of Business (University of Western Ontario) and foundedSAGEMedicalConsultantsInc.,aprivatelyownedbiotechnologycompany.

Dr.MarignanijoinedDalhousieUniversityin2003,andiscurrentlyaProfessorin theDepartmentofBiochemistryandMolecularBiology,andDirectorofthe Pipeline-2-PrecisionMedicine CancerWave initiative in the Faculty ofMedicineatDalhousieUniversity.Dr.Marignaniandherteamdiscoverednewcombinationtherapiesforthetreatmentofoncogene-specificbreastcancerinspontaneousmousemodelsofbreastcancer.ShehasalsodevelopedanewCRISPR-Cas9mousemodelof lung cancer thatwill beused fordevelopingmorepreciseandtargetedtreatmentsfortheleadingcauseofcancer-relateddeathsamongCanadians.

Dr.Marignani’sdiscoverieshavebeenhighlightedbyRadioCanada,GlobalTV,CTV,CBC, in EuropeandAsiannews sources, aswell as inprint news.Dr.Marignanitrainsandmentorsthenextgenerationofscientistsincludinggrade school students, undergraduate, graduateandpost-doctoral fellows,andisactivelyinvolvedincommunityoutreachandeducation.Dr.Marignaniis the Founder of CanadianWomen in STEM, a not-for-profit organizationfocussed on improving equity, diversity and inclusivity for all people inSTEMdisciplines.Dr.Marignani isworking towardsbringingAthenaSwan/SeaChange-likeprogramstoCanadianuniversities.

Formore informationaboutDr.Marignani,pleasevisit www.marignanilab.comandfollowheronTwitter@pmarignani@CDNWomenSTEM

Dr. Paola Marignani


Dr. Nafisa M. Jadavji, Councillor, Trainee RepresentativeNafisa Jadavji is a neuroscientist, post-doctoral fellow researcher andinstructoratCarletonUniversityandtheUniversityofOttawa.ShecompletedherdoctoraltrainingatMcGillUniversityinMontréal,andherpost-doctoraltrainingattheCharitéMedicalUniversityinBerlin,Germany.Herpost-doctoralresearchfocussesonunderstandinghowdietaryandgeneticdeficienciesinone carbonmetabolism, specifically folatemetabolism, affect neurologicalfunctionoverthelifespanusingamousemodel.Dr.JadavjihasbeenfundedbytheFederationofEuropeanNeuroscienceSociety(Europe),NeuroWIND(Germany), the Canadian Association for Neuroscience, the CanadianInstitutes of Health Research (CIHR), the Natural Sciences & EngineeringResearch Council (NSERC), the International Brain Research Organization,theParkinson’sDiseaseFoundation(US),theBurroughsWellcomeFund(US)andFondsdelarecherchéensantéQuébec.SheistheChairoftheBoardofDirectorsfortheJournalofYoungInvestigators(JYI),anonlineinternationalundergraduatepeer-reviewedjournal.

AstheCSMBpost-doctoralrepresentativeandchairofthetraineecommittee,Nafisa hopes to bring her experiences in leadership and research to theposition.HergoalwhileinthispositionistoincreasethevisibilityofCSMBforCanadiantrainees.ShealsoplanstoenhancethetraineeexperienceforCSMBmembersbydevelopingmoretrainee-orientedprograms.

Bensun Fong, Councillor, Trainee RepresentativeBensun Fong, B.Sc (2013) is a Ph.D. Candidate in Cellular and MolecularMedicineattheUniversityofOttawa,underthesupervisionofDr.RuthSlack.HisresearchfocussesontheinvolvementofRbFamilyproteinsintheregulationofneuralstemcellfateduringdevelopmentandadultneurogenesis.BensunisarecipientofanOntarioGraduateScholarship.

As a CSMB graduate student representative, Bensun aims to increase thevisibilityofCanadiangraduatestudentsinmolecularbiosciencesadvocatingfor support of fundamental research, and to increase opportunities andeventsthatsupportcollaborationbetweenCSMBtraineemembers.

Dr.NafisaM.Jadavji

Bensun Fong


Minutes of the 60th Annual General Meeting 2017 Ottawa, Ontario – 19 May 2017

Attendees: Randal Johnston; Roberto Botelho; Tarik Möröy; Charles Vadnais; Mireille Khacho; Rebecca Shapiro; Bensun Fong; Trang Pham; Logan Donaldson; Jim Davie; Phil Hieter; Christian Baron; Jan Rainey; Kristin Baetz; Vince Tropepe; Stef Bennett; Paula Adler; Martine Jaworski; Daniel Serrano; Marc Coppolino; Kin Chan; Frances Sharom; Jason Tanny; Amy Caudy; Martin Duennwald; Costin Antonescu; Paolo Marignani; H.J. Wieden; Vincent Archambault; Jean Francois Couture; Vanina Zaremberg; Sabine Elowe; Barbara Karten

1. Greetings from the President (Baetz) – Power Point PresentationBaetzwelcomedCSMBmembersandgueststotheAGM.Shebeganhercommentswiththeaidofaslideshow,andemphasizedtheimportanceoftheeffortsoftheCSMBintheareaofadvocacyonbehalfoffundamentalscienceonParliamentHill,togetherwithourpartnersResearchCanadaandPAGSE.AmajorthrustwheresignsofsuccessareevidentisinplannedreformswithCIHR.Mediaattentionhasbeenverypositive,withproposedchangestothecompetitivefundingmodel,governingcouncil,anddiversity/innovation/inclusion.Wenowarguablyhavetheearofgovernment.Amajorefforthasbeenonthedouble/doublecampaignandpetitionforenhancedfunding,plusHillTimesads.CSMBhasemployedtheResearchCanadapressreleaseservice,whichisinexpensiveandefficient.ThenextroundoffocuswillbetogeneratesupportfortheNaylorreport-getitofftheshelf!Finally,researchersmustuniteinoursupportandnotwastetimeandenergycriticizingsmalldetails,butfocusonthebigpicture.

2. Approval of Quorum and AgendaApprovalofquorumandagenda:Johnston(moved)andRainey(seconded),approvedunanimously.

3. Approval of the Minutes of 59th Annual General Meeting in Vancouver, July 20, 2016HieterandMöröymovedandseconded,approvedunanimously.

4. Business arising from the minutes (Johnston)Johnstonexplainedthatallitemsinthepreviousminuteswereupheldoractedupon,withtheexceptionsthata)electronicvotingwasnotactivatedforthepresentmeetingaspreviouslyhoped;andb)theoriginallargepotentialdeficit fromthe2016Vancouvermeetingofapproximately$240Khadbeengreatlyreducedtoapproximately$60K,whichwasstilllarge,butnolongerthreatenedthecontinuedoperationsofCSMB.

5. Secretary’s Report (Johnston)Membership goal:Membership has stopped declining, and possibly is beginning to increase as our advocacyeffortshaveincreasingimpact.Westillneedtoemphasizegreaternumbersofregularpaidmemberships,whichremainaround200.

6. Treasurer’s Report (Rainey)(a) PresentationoftheAccountant’sReviewedFinancialStatement.(b) Afinanciallossduetothe2016IUBMBVancouverconferenceandthe2018ICGcancellationhasledtoasignificant

decreaseinCSMBreserves.(c) Effortsareunderway tominimizecosts (Bulletinproduction/mailing; reducedawardsand travel support,etc.),


andincreaserevenue(thecurrentOttawameetingisexpectedtomakeasignificantprofit),plusexpandadvocacyefforts.

(d) Acceptance of the Reviewed Financial Statement (2016): Rainey and Möröy; approved unanimously.(e) ApprovalofSigningOfficers:Rainey tocontinueasTreasurerandSigningOfficer;Davie to replace Johnstonas

GeneralSecretaryandSigningOfficer,witha6-monthtransitionperiod.RaineyandHieter;approvedunanimously.

7. Board Membership for 2016 - 2017 (Baron)Baron reviewed the submitted candidates; he was assisted in the Nominations Committee by members AndrewSimmondsandSteffanyBennett.BaronremindedCSMBmembersthattheBoardstructureincludestrainees;Directorsareappointedfor2-yearterms,renewable.ForthisyearwehaveDonaldsonsteppingdownasaDirector;NodwellandBaronwishtorenewtheirrolesasDirectorsfor2moreyears;JohnstonissteppingdownasGeneralSecretary;HieterwillmovefromPresident-Elect toPresident;BaetzwillmovefromPresidenttoPast-President;MöröyagreestobenominatedasPresident-Elect;JimDavieisproposedasGeneralSecretary;traineesFongandJadavjiareproposedasnewTraineememberstoreplaceVoronovaandLhor;MarignaniisproposedasanewDirectortoreplaceDonaldson;a) CallfornominationsfromtheFloor:BaroninvitedCSMBmembersthatwerepresentforanyadditionalnominations;

nonereceived.b) Councillors and Executive; Baron and Baetz recommended the slate described above for approval; approved

unanimously.

8. Board Committees and call for volunteersBaetz described the Board structure and its proposed updated or new committees. Themandates of the variouscommitteesweredescribed,andsheencouragedmembersat large (including trainees) toconsider servingon thecommittees so that diversity andmomentum can both be enhanced. The identified committees are: Advocacy&Communications;Membership&Diversity;Finance&Development;Awards;Nominations;Trainee;Conferences.

9. Meeting Reportsa)PresentationofproposedCSMBMeetingGuidelines:BaetzofferedthefollowingrecommendationsforfutureCSMB

conferences:theyshouldbediverse intopicsorareasof focus,plus inclusiveofadiversegroupofparticipants;presentations should include selections fromsubmittedabstracts; efforts shouldbemade to includewomen inbothorganizationandpresentation;inexpensive;accessiblelocations;rotatevenuesamongpopularsites;employexperiencedorganizers;controltravelcosts;identifysponsorsforawardsandotherspecialactivitiesorspeakers;Boardcostsshouldbeconsideredseparatelyfromconferencecosts.

b)2017:Ottawa(Baetz)CelebratingCanadianMolecularBiosciencesMay16-20,2017.422participantsareregistered,whichisoneofthehighestamongregularCSMBconferences;81talkswerepresented,ofwhich60%wereselectedfromabstracts;$120Kraisedfromregistrationfees;$44Kreceivedfromsponsors;anticipateprofitof~$40K(includingHSTreturn),whichisabigimprovementfrompreviousmeetings,andamodelforfutureCSMBconferences.

c) April11-15,2018:Banff(Johnston)MembraneProteinsinHealthandDiseaseHowardYoungistheprincipalorganizer,forameetingthatrecurseveryfiveyears.Majorspeakersalreadyconfirmed.

d)CallforOrganizers:CSMBConferencein2019PossiblelocationwillbeinMontreal,perhapsatUdeMontreal;MöröyandBaronwillestablishasmallteamtoconsidervenuesandthemeandwillreporttotheCSMBBoardinSeptember.

10. Other Business/Adjournment Nootherbusinesswasidentifiedfordiscussion,andthemeetingadjournedtoenableageneraldiscussionamongthoseattendingregardingAdvocacyStrategyandhowtoenhancemembership.


Independent Practitioner’s Review Engagement Report

TotheMembersoftheCanadianSocietyforMolecularBiosciences

IhavereviewedtheaccompanyingfinancialstatementsofCanadianSocietyforMolecularBiosciencesthatcomprisethestatementoffinancialpositionasatDecember31,2017,andthestatementsofoperationsandchangesinnetassetsandcashflowsfortheyearthenended,andasummaryofsignificantaccountingpoliciesandotherexplanatoryinformation.

Management’sResponsibilityfortheFinancialStatementsManagement is responsible for thepreparationand fair presentationof thesefinancial statements in accordancewithCanadianaccounting standards fornot-for-profitorganizations, and for such internal control asmanagementdeterminesisnecessarytoenablethepreparationoffinancialstatementsthatarefreefrommaterialmisstatement,whetherduetofraudorerror.

Practitioner’sResponsibilityMyresponsibilityistoexpressaconclusionontheaccompanyingfinancialstatementsbasedonmyreview.IconductedmyreviewinaccordancewithCanadiangenerallyacceptedstandardsforreviewengagements,whichrequiremetocomplywithrelevantethicalrequirements.

AreviewoffinancialstatementsinaccordancewithCanadiangenerallyacceptedstandardsforreviewengagementsisa limitedassuranceengagement.Thepractitionerperformsprocedures,primarily consistingofmaking inquiriesofmanagementandotherswithintheentity,asappropriate,andapplyinganalyticalprocedures,andevaluatestheevidenceobtained.

Theproceduresperformedinareviewaresubstantiallylessinextentthan,andvaryinnaturefrom,thoseperformedinanauditconductedinaccordancewithCanadiangenerallyacceptedauditingstandards.Accordingly,Idonotexpressanauditopiniononthesefinancialstatements.

ConclusionBasedonmyreview,nothinghascometomyattentionthatcausesmetobelievethatthefinancialstatementsdonotpresentfairly,inallmaterialrespects,thefinancialpositionofCanadianSocietyforMolecularBiosciencesasatDecember31,2017,andtheresultsofitsoperationsanditscashflowsfortheyearthenendedinaccordancewithCanadianaccountingstandardsfornot-for-profitorganizations.

NumerisCPACharteredProfessionalAccountant LicensedPublicAccountantOttawa,OntarioApril11,2018


CANADIAN SOCIETY FOR MOLECULAR BIOSCIENCES

Financial Statement

STATEMENT OF FINANCIAL POSITION

AsatDecember31,2017UNAUDITED

2017 2016

ASSETS

CURRENTCash $9,861 $ 9,646

Marketablesecurities-shortterm(note3) 236,115 211,898

Accountsreceivable 50,789 35,492

Prepaidexpenses 25,032 38,410

$321,797 $295,446

LIABILITIES

CURRENTAccountspayableandaccruedliabilities $6,163 $12,150

Deferredmembershipfees-shortterm 3,259 3,343

9,422 15,493

DEFERRED MEMBERSHIP FEES - LONG TERM 5,774 5,337

15,196 20,830

306,601 274,616

BALANCE $321,797 $295,446


STATEMENT OF OPERATIONS AND CHANGES IN NET ASSETSYearendedDecember31,2017UNAUDITED

2017 2016

REVENUESAnnualmeetingrevenue $237,078 $570,820

Membershipfees 33,236 23,075Investmentincome 4,015 10,282Miscellaneous 425 2,796

$274,754 $606,973

EXPENDITURESAnnualconferenceexpenses 208,660 628,507

Boardmeetingsandtravel 13,134 18,111Secretariat 10,573 18,763Website 4,975 12,907Fundingandothersponsorship 2,500 13,000Scienceadvocacy 2,350 2,325Bank,creditcard,andinvestmentmanagementfees 1,712 1,763Bulletin 1,646 15,896Accountingfees 4,806 5,312Insurance 750 5,250Officeexpenses 474 510

251,580 722,344

DEFICIENCY OF REVENUES OVER EXPENDITURES BEFORE OTHER ITEMS 23,174 (115,371)

OTHER INCOMEGainonsaleofmarketablesecurities 1,173 26,684

DEFICIENCY OF REVENUES OVER EXPENDITURES (24,347) (88,687)

NET UNREALIZED GAIN ON MARKETABLE SECURITIES 7,638 447

DEFICIENCY OF REVENUES OVER EXPENDITURES 31,985 (89,134)

BALANCE, BEGINNING OF YEAR 274,616 363,750

BALANCE, END OF YEAR $306,601 $274,616


STATEMENT OF CASH FLOWSYearendedDecember31,2017UNAUDITED

2017 2016

OPERATING ACTIVITIESExcess(deficiency)ofrevenuesoverexpenditures $31,985 $ (89,134)Adjustmentforgainonsaleofmarketablesecurities (1,173) (26,684)

30,812 (115,818)

Changeinnon-cashworkingcapitalitemsMarketablesecurities–shortterm (23,044) 164,907Accountsreceivable (15,297) (31,149)Prepaidexpenses 13,378 (22,853)Accountspayableandaccruedliabilities (5,987) (3,467)Deferredmembershipfees–shortterm (84) 867

(222) (7,513)

FINANCING ACTIVITYDeferredmembershipfees-longterm 437 1,559

NET (DECREASE) INCREASE IN CASH 215 (5,954)

CASH, BEGINNING OF YEAR9,646 15,600

CASH, END OF YEAR $9,861 $ 9,646


NOTES TO THE FINANCIAL STATEMENTS

DECEMBER 31, 2017, UNAUDITED

1. NATURE OF OPERATIONS

CanadianSocietyforMolecularBiosciences(wasincorporatedwithoutsharecapitalin1979underPartIIoftheCanadaCorporationsActandisrecognizedasanot-for-profitorganizationforincometaxpurposes.ThemainobjectiveoftheSocietyistofosterresearchandeducationinthemolecularbiosciencesinCanada.

2. SIGNIFICANT ACCOUNTING POLICIES

TheorganizationappliestheCanadianaccountingstandardsfornot-for-profitorganizations.

(a) Revenue recognition

Theorganizationfollowsthedeferralmethodofaccountingforcontributions.Restrictedcontributionsare recognizedas revenue in theyear inwhich therelatedexpendituresare incurred.Unrestrictedcontributionsarerecognizedasrevenuewhenreceivedorreceivableiftheamounttobereceivedcanbereasonablyestimatedandcollectionisreasonablyassured.

(b) Capital assets

Capital assetspurchasedatacostofless than $2,000 are expensed in the year ofpurchase.TheSocietydoesnotowncapitalassetsatthistime.

(c) Use of estimatesThepreparationoffinancial statements inconformitywithCanadianaccountingstandards for not-for-profit organizations requires management to make estimates and assumptions that affect thereported amounts of assets and liabilities at the date of the financial statements and the reportedamounts of revenues and expenses during the reporting period. By their nature, these estimatesare subject to measurement uncertainty. The effect of changes in suchestimatesonthefinancialstatementsinfutureperiodscouldbesignificant.

(d) Financial instruments

TheSocietyinitiallymeasuresitsfinancialassetsandfinancialliabilitiesatfairvalue.

TheSocietysubsequentlymeasures all itsfinancialassetsandfinancial liabilitiesat amortized cost,except for investments in equity instruments that are quoted in an active market, which aremeasured at fair value.Changes in fair value are recognized in the statementofoperations.

Financialassetsmeasuredatamortizedcostincludecashandaccountsreceivable. Financialliabilitiesmeasured at amortized cost include accounts payable. The organization’s financial assets measured atfairvalueincludequotedshares.


3. MARKETABLE SECURITIES – SHORT TERM

CSMB investments are recordedatmarket value. As requiredbyCICASection3856unrealized gains or lossesontheportfolioasawholeatDecember31arerecordedas“Netunrealizedgains on marketablesecurities” and included on the Statement of Operations and Changes in Net Assets.

AllamountsbelowarequotedinCanadiandollars.

2017 2016Cashandshortterminvestments 379 978Fixedincome 82,261 73,300Commonequity 87,137 77,248Cashandshortterminvestments(USaccount) 2,811 424Commonequity(USaccount) 63,527 59,948

$236,115 $211,898

4. ANNUAL CONFERENCE EXPENSES

2017 2016Exhibitandfacilityexpenses 153,877 155,547Receptionsandbanquets 30,680 18,656Speakerstravelandexpenses 11,954 204,027Awards 5,426 1,301Meetingorganizerfees - 111,794Suppliesandother 6,723 137,182

$208,660 $628,507

5. FINANCIAL INSTRUMENTS RISKS AND UNCERTAINTIES

Theorganization’sfinancialinstrumentsconsistofcash,short-terminvestment,accounts receivable,andaccounts payable and accrued liabilities.Unless otherwise noted, it is management’s opinion that theorganizationisnotexposedtosignificantinterestrate,currency, credit,liquidityorcashflowrisks.Thefairvalueofthesefinancialinstrumentsapproximatetheir carryingvalues,unlessotherwisenoted.

Marketriskistheriskthatthevalueofafinancialinstrumentwillfluctuateasaresultofchangesin marketprices,whether the factors are specific to the instrumentor all instruments traded in the market.TheCSMBisexposedtomarketriskduetothevolatilenatureofequityinvestments.


Meeting Report: The 60th Annual Meeting of the CSMB

Celebrating Canadian Molecular Biosciences – from Organelles to Systems Biology

The 60th Annual Meeting of the Canadian Society forMolecularBioscienceswasheldMay16-202017attheShawCentreindowntownOttawa,locatedclosetotheRideauCanal,andwithgreatviewsoverParliamentHillandotherhistoricbuildings inournation’s capital. Theconferencewasattendedbyover400researchersfromacrossCanadaandtheU.S.,andwasdesignedtoprovideaccesstothespecialeventstakingplaceinOttawaduring2017,whichwasCanada’s150thbirthday.

OverviewCSMB 2017 was organized in a different format frompreviousmeetings,offeringmultiplesynergisticresearchthemes,with the aim of attracting a larger number ofattendees. A commitment was also made to embraceEquity, Diversity and Inclusivity (EDI), and the slate ofspeakers reflected the diversity of our membership,with over 50% being women and visible minorities.Halfthespeakerswereinvited,andtheotherhalfwerechosen from the submitted abstracts, which ensuredthatscientistsatallstagesoftheircareerswereabletocommunicatetheirresearchfindingstoalargeaudience.

The conference by jointly organized by researchersprimarily at the University of Ottawa/Ottawa Institute

of Systems Biology and Ryerson University; the LocalOrganizing Committee included Kristin Baetz (Ottawa,Co-Chair), Costin Antonescu (Ryerson, Co-Chair), Jean-François Couture (Ottawa), Roberto Botelho (Ryerson),Michael Downey (Ottawa) and Gregory Fairn (St.Michael’sHospitalandtheUniversityofToronto).

The conference was structured around 16 parallelsessions (8 in Organelle Biology and 8 in SystemsBiology),fourSpecialJointSessions,threeawardlecturesandfourspecialpurposeTraineeWorkshops.Overall,83oralpresentationsweregivenover thefivedaysof theconference, by both internationally-known researchersandtrainees.

The Annual General Meeting of the CSMB was heldduring the conference, and focussed on the past andfutureactivitiesofthesocietyonbehalfofitsmembers,especiallyitsworktopushforwardtherecommendationsoftheNaylorFundamentalScienceReviewregardingtheorganizationandfundingofscientificresearchinCanada.Optimismwasexpressed that themessagewasgettingthroughtoparliamentariansintheTrudeaugovernment.

Dr.FrancesJ.SharomBulletinEditor,CanadianSocietyforMolecularBiosciencesProfessorEmeritus,DepartmentofMolecularandCellularBiology,UniversityofGuelph


Meeting sessionsThemainpartoftheconferenceopenedwiththeKeynoteLecture and Jeanne Manery Fisher Memorial Lecture,givenbyDr.BrendaAndrews,DepartmentofMolecularGenetics at the University of Toronto. Dr Andrewsdescribedhowhergroupusedsyntheticgeneticarraystocompleteareferencegeneticinteractionmapforyeast,resultinginthelargestdynamicbiologicalnetworkofitskind, essentially a geneticwiring diagram of the yeastcell. The lecture was followed by an open reception,whichwasalsoattendedby localMPsofseveralCSMBmembers,whichledtoongoingdiscussionofissuesandfuturegoalsintheCanadiansciencefundinglandscape.

The8scientificsessionsintheOrganelleBiologythemecovered the topics Membrane Trafficking and Sorting;Trafficking and Development; Membrane Trafficking inCancer; Stress, Metabolism and Trafficking; TraffickingandLipidSignalling;Pathogens;OrganelleContacts;andOrganelleIdentityandBiogenesis.

The Systems Biology of Neurobiology; RegenerativeMedicine; Models of Rare Diseases; Biological andSyntheticNetworkAnalysis:fromHairballstoKnowledge;Metabolomics and Metabolic Diseases; the MicrobialWorld; Emerging Signalling Pathways; and Epigeneticsmadeupthe8sessionsincludedintheSystemsBiologytheme.

Eachsessionhadatleastoneinvitedspeaker,andallthesessionsweretimedtoallowattendeestomovebetweentheparallel sessions, so that they couldattend talks ineachtheme.

The four Special Joint Sessions were organizedaround topics of interest to all conference attendees,and covered Cancer Biology, Spatial Organization ofRegulatoryNetworks,andendedwithNewTechnology,andSyntheticBiologyandBeyond,onthefinalmorningofthemeeting.

Award lecturesInadditiontotheJeanneManeryFisherMemorialAwardlecture,deliveredbyBrendaAndrews(seeabove),SergioGrinstein (Hospital for Sick Children and theUniversityof Toronto), received the Canadian Science PublishingSenior Investigator Award, and delivered a fascinatingtalk onhow receptors and integrins interactwith boththe cytoskeleton and the exoskeleton to initiate the

process of phagocytosis. The last award lecture,whichwasscheduledinthefinaltime-slotofthemeetingwasdelivered by Martin Schmeing of the Department ofBiochemistry,McGillUniversity,whowowedtheaudiencewithmusicallyaccompaniedconformationalchanges,ashedescribedthestructuralbiologyofafascinatinggroupof nonribosomal peptide synthetases. Dr. Schmeingreceived the CSMB New Investigator Award. This wasa suitablyhighnoteonwhich toenda very successfulmeeting.

Trainee eventsTheCSMBiscommittedtoofferingvalue-addedeventsforour traineesat theannualmeeting,andagroupoftrainee organizers, led by Victoria Hipolita (Ryerson),Trang Pham (Ottawa),Maneka Chitiprolu (Ottawa) andKelseyLaw(Toronto)didanamazing jobat theOttawameeting.TheafternoonofMay16wasdevotedtofourtraineeworkshops, andwas followed by a networkingevent,allheldattheUniversityofOttawa.Theafternoonkicked offwith two simultaneous 1-hour sessions, oneentitled“StrategicCommunications:MarketingYourselfasa Trainee for YourDreamCareer”, ledbyDrs.NanaLee and Reinhart Reithmeier from the Department ofBiochemistry at the University of Toronto. The othersession was devoted to “Supporting the ProfessionalDevelopment of Women in STEM”, and was led byCatherine Tsilfidis, Director of the Office of Equity,DiversityandGenderIssues,FacultyofMedicine,attheUniversityofOttawa,Dr.ImogenCoe,DeanofScienceatRyersonUniversity,andAriadniAthanassiadis,a lawyerwith Kyma Professional Corporation, and President ofWISEOttawa.

Afteracoffeebreak,thecareersthemecontinuedwithaworkshopon“PI/PDFHunting:PreparingFutureFaculty”, ledbyagroupof facultymembers fromtheUniversityof Ottawa; Assistant ProfessorMike Downey, AssistantProfessor Mathieu Lavalle-Adam, Daniel Figeys, Chairof the Department of Biochemistry, Microbiology andImmunology,andDavidLohnes,ChairoftheDepartmentofCellularandMolecularMedicine.

Adiversegroupof scientists fromgovernment, variousagencies and the private sector presented alternativesto academia in “Alternative Career Options in Science:Not soAlternativeAnymore”,withDeborahGordon-EI-Bihbety (President of Research Canada), Linda Harris(Scientist with Agriculture and Agri-Food Canada),


Michael Donaldson (Content Development Manager,Canadian Science Publishing), Rafal lwasiow (Vice-President, Research & Development at DNA Genotek),Sabrina Kim (Sector Analyst, Innovation, Science &EconomicDevelopmentCanada),AngelaYeung(ProgramOfficeratNSERC),andCarmenGervais(ProgramDeputyDirector,NetworkofCentresofExcellence/NSERC).

All the sessions were very well-attended, and werefollowedbyaTraineeNetworkingevent,wheretraineesmingledandtalkedwiththeworkshopinvitedspeakers.Later that evening, a Trainee Pub Night (to which allconference registrants were invited) was held at TheLieutenant’s Pumpon Elgin Street,where a good timewashadbyall.

Poster sessionsAlargenumberofposterswerepresentedatthemeeting(117 intotal)spreadovertwoseparatepostersessionsonWednesday and Thursday afternoons. Themajorityof the posters were presented by graduate and post-doctoral traineesandmuch livelydiscussionensued.AteamofvolunteerjudgesvisitedallthepostersthathadbeenenteredintheCSMBpostercompetition,andtheauthorswereasked toexplain their research in abriefpresentation. Itwasadifficulttask,giventheveryhighqualityofthepostersoverall,butseveralwerejudgedtobeoutstandingandwereawardedprizes:Nina Ahlskog:M.Sc. student, University of Ottawa/TheOttawa Hospital Research Institute (Richard Bergeron’sgroup)Matthew Berg: Ph.D. student, Department ofBiochemistry, University of Western Ontario (ChrisBrandl’sgroup)Alexanne Cuillerier: Ph.D. student, Department ofCellular andMolecularMedicine, University of Ottawa(YanBurelle’sgroup)Roni Levin: Ph.D. student, Hospital for Sick Children/UniversityofToronto(SergioGrinstein’sgroup)EmmaSmith:M.Sc.student,Queens’sCancerResearchInstitute and Department of Pathology & MolecularMedicine,Queen’sUniversity(SusanCole’sgroup)

Enjoying OttawaConferenceattendeeswereabletotakeadvantageofthemuseums,theNationalGallery,andmanyotheractivitiesonofferinOttawa,aswellasthethousandsofcolourfultulipsondisplay inflowerbedsaroundthecityaspartoftheannualTulipFestival.TheBrewDonkeybeertour

heldinthefree-timeafternoonwascompletelysoldout!

Thelasteveningoftheconferencewaspartynight,withalavishbuffetbanquetheldattheCanadianMuseumofNature,surroundedbydinosaursandsomeoftheaward-winning nature photos from the Canadian GeographicWildlife Photography of the Year 2015 competition.The identity of the poster prizewinnerswas revealed,and their awards were presented, to much applause.Everyone was impressed with the fabulous band, thePepTides(https://www.thepeptides.com/),whokeptthedancefloorpackedand theaudience rockinguntil lateintotheevening.

Sponsors and exhibitorsFinally, the conference benefited greatly from five platinum sponsors (the Canadian Institutes for HealthResearch, Canadian Science Publishing, RyersonUniversity Faculty of Science, the Ottawa Institute ofSystems Biology and the University of Ottawa), fivegold sponsors (AvantiPolar Lipids, theOttawaHospitalResearch Institute, Scientific Reports, StemCoreLaboratories and ThermoFisher), three silver sponsors(the Rare Diseases: Models & Mechanisms Network,Traffic, and Wiley), as well as the Genetics Society ofAmerica and the International Journal of MolecularSciences.

We also thank our exhibitors, including AgilentTechnologies, GE Healthcare, Qiagen and Quorum,whobenefittedfromboothspaces locatedclosetothemany poster presentations where coffee breaks andrefreshmentswereprovided.


Scenes from the 60th Annual Meeting Ottawa, 2017

TheconferencebanquetandtraineeawardspresentationwasheldattheCanadianMuseumofNature

TheShawCentreinOttawa

ParticipantsintheconferencecouldenjoythethousandsofcolourfultulipsondisplayaspartoftheannualOttawaTulipFestival


Apanelofscientistsfromgovernment,variousagenciesandtheprivatesectorledatraineeworkshopon“AlternativeCareerOptionsinScience:NotSoAlternativeAnymore”

Dr.NanaLee(UniversityofToronto)leads a trainee workshop on “Strategic Communications:MarketingYourselfasaTraineeforYourDreamCareer”

Thetraineeworkshopswereverywellattended

Atraineeworkshopon“PI/PDFHunting:PreparingFutureFaculty”wasledbyseveralfacultymembersfromtheUniversityofOttawa.

ThemeetingwasopenedbyconferenceCo-ChairsDrs.KristinBaetz(UniversityofOttawa)andCostinAntonescu(RyersonUniversity)


Dr.KristinBates,PresidentoftheCSMB,congratulatesDr.MartinSchmeing(McGillUniversity),winneroftheCSMBNewInvestigatorAward”

KeynoteLecturerDr.BrendaAndrews(UniversityofToronto)receivestheJeanneManeryFisherMemorialAwardfromDr.KristinBaetz,PresidentoftheCSMB

Dr.MartinSchmeingdelivershisconferencetalk

Dr.BrendaAndrews(UniversityofToronto)introducing her talk at the podium

ConferenceattendeesattheopeningreceptionintheShawCentre


LloydLongfield(centre),LiberalMPfortheGuelphriding,chattingwithUniversityofGuelphconferenceattendees,Dr.NinaJones(left)andDr.FrancesSharom(right)

Dr.ImogenCoe(RyersonUniversity)attheopeningreception

Discussions at the poster sessions


Conferenceattendeespresentingtheirtalks

CanadianSciencePublishing,aPlatinumSponsorofthe2017meeting

AgilentTechnologies,oneoftheconferenceexhibitors


Attheconferencebanquet,attendeespartiedwith the dinosaurs

Qiagen,oneoftheconferenceexhibitors

Invitrogen,oneoftheconferenceexhibitors

NinaAhlskogreceivesanawardforherposterpresentation

GEHealthcareLifeSciences,oneoftheconferenceexhibitors

ThermoFisher,aGoldSponsorofthe2017meeting


AlexanneCuillerierreceivesanawardforherposterpresentation

RoniLevinreceivesanawardforhisposterpresentation

HighenergyperformancebythePepTides

MatthewBergreceivesanawardforhisposterpresentation

ThePepTidesentertainedthecrowdfortheevening


Dr.H.J.Wieden(UniversityofLethbridge)giveshistalkinthefinalSpecialJointSessionon“SyntheticBiologyandBeyond”

Dr.JefBoeke(NewYorkUniversitySchoolofMedicine)giveshistalkinthefinalSpecialJointSessionon“SyntheticBiologyandBeyond”

Thedancefloorwaspackedformuchoftheevening


Trainee Committee Activities 2017CSMB Trainee Committee Twitter CampaignThe significantly increased investments in fundamentalscienceannouncedinthe2018FederalBudgetcouldnothave been possiblewithout the unified and consistentvoiceofresearchersatallcareerstages.Wewould liketosayTHANKYOU!toallthegraduatestudentsandpost-docswhoparticipatedintheCSMB#NextGenCanScienceTwittercampaigninthesummerof2017,forputtingover150facestothenextgenerationofCanadianresearchersacknowledgedbythisbudget.

Whilethereismuchfortraineestocelebrate,Budget2018 notably did not commit funding to the Vanier-

Bantingscholarships.AsCanada’sFundamentalScienceReviewrecommendeda“totalbase increaseof$140mperyearbephasedinoverfouryears,inequalincrementsof $35m per year”, we look forward to forthcomingconsultationsoverthenextyear.

TheTraineeCommitteeofCSMBcontinuestoadvocateforincreasedinvestmentsthatbetterrecruit,supportandretaintraineesinmolecularbiosciencesacrossCanada.

BensungFongB.Sc.andDr.NafisaM.JadavjiCSMBTraineeRepresentatives

.

Collageofthemanyimagesoftraineestweetedunderthehashtag#NextGenCanScience


2018 CSMB Award DesignatesCSMB New Investigator AwardTheCSMBNewInvestigatorAwardrecognizesmeritoriousresearchinoneormoreofthefieldsofbiochemistry,molecularorcellularbiologyinCanada.Recipientshavetenyearsorlessofindependentresearchexperience,anddemonstrateoutstandingresearchaccomplishments.

Dr. Katey RaynerUniversity of OttawaKateyRaynerisanAssistantProfessorattheUniversityofOttawaHeartInstitutein the Department of Biochemistry,Microbiology and Immunology, whereshe directs the CardiometabolicmicroRNALaboratory.SheobtainedherB.Sc.fromtheUniversityofToronto,andherPh.D.fromtheUniversityofOttawa.Dr. Rayner’s doctoral work focussedon the role of hormones, heat shockproteins and macrophage foam cellsin the development of atherosclerosis.After her Ph.D., she pursued apost-doctoral fellowship, first atMassachusettsGeneralHospitalthenatNewYorkUniversitySchoolofMedicine,where Dr. Rayner helped to discovera role for microRNAs, specificallymicroRNA-33, in the regulation of HDLanditsatheroprotectiveeffects.

SinceestablishingherlabattheUniversityofOttawa,Dr.Rayner’sresearchprogramfocusses on novel mechanisms thatunderlietheinflammatoryprocessesofplaque progression and vulnerability,withaspecificfocusontheintersectionbetween macrophage inflammation

and microRNAs as drivers of disease.Her group has uncovered a novel rolefor microRNA control of mitochondrialrespiration in macrophage cholesterolefflux. Dr. Rayner’s research alsoexamines how extracellular microRNAsare mediating the progression ofatherosclerosis in both human andanimal models. More recently, hergroupuncoveredaroleforprogrammednecrosisinthedevelopmentofunstableplaques inmiceandhowthis canbeatherapeuticanddiagnosticbiomarkerinhumans.

Dr. Rayner has been recognized withawards such as the American HeartAssociation’s Irvine H. Page YoungInvestigatorAward,theEarlyResearcherAward from theMinistry of InnovationOntario, and New Investigator Awardsfrom both the Canadian Institutes forHealth Research and the Heart andStrokeFoundation.Dr.Rayner’sresearchis currently funded by the CanadianInstitutesforHealthResearch,theHeartand Stroke Foundation of Canada andtheNationalInstitutesofHealth.


NRC Research PressSenior Investigator AwardThisawardrecognizesarecordofoutstandingachievementinresearchinoneormore of the fields of biochemistry,molecular or cellular biology, undertaken inCanadabyaCanadianscientist.

Dr. Richard RachubinskiUniversity of AlbertaRichardRachubinski isaDistinguishedUniversity Professor and Chair of theDepartment of Cell Biology, Facultyof Medicine and Dentistry, at theUniversityofAlberta.Rickisnowinhisfifth five-year term, and has excelledin research, department building andadministration,mentoring of researchtrainees and service to the scientificcommunity.

Dr.Rachubinskihasbeen investigatingand elucidating the molecules andmechanismscontrollingthebiogenesisof peroxisomes, membrane-enclosedorganellesinvolvedinlipidmetabolismand the detoxification of reactiveoxygen species. Peroxisomes areessential for human survival, a factunderscored by the existence of anumberofinheritedgeneticdisorders,collectively called the peroxisomebiogenesis disorders (PBDs), resultingfrom dysfunction of peroxisomebiogenesis. Dr. Rachubinski hasdefined how peroxisomes are madeincells, identifiedandcharacterizedanumberofgenes(PEXgenes)requiredfor peroxisome biogenesis whosemutation causes the PBDs, elucidatedhow peroxisomes are inherited bycellstomaintainthebenefitsofhavingperoxisomes, and developed aninsectmodel of the PBDs that allowsfor the rapid screening of potential

therapeuticstotreatthedisorders.

Dr. Rachubinski was an MRCPostdoctoral Fellow, Scholar, Scientistand Senior Scientist; a HowardHughesMedicalInstituteInternationalResearch Scholar (three terms); anda Tier I CanadaResearchChair inCellBiology. He is a Fellow of the RoyalSociety of Canada, the CanadianAcademy of Health Sciences, andthe American Association for theAdvancement of Science. He receivedthe Royal Society of Canada’s QueenElizabeth IIDiamond JubileeMedal in2013.

Dr. Rachubinski served as a memberof the Advisory Board of the CIHRInstituteofGenetics,amemberoftheMedicalAdvisoryBoardoftheCanadaGairdner Foundation and co-chair oftheFoundation’sMedicalReviewPanel.In2010and2012hewasChairoftheGenomics Research in Human HealthCommitteeforGenomeCanada.

Dr.Rachubinski’sworkisinternationallyrecognizedandhasbeeninstrumentalin taking what was once a ratherobscure organelle, with obscurediseasesaboutwhichlittlewasknown,andcatapultingitintothemainstreamof both basic scientific and clinicalinvestigation.


TheCSMBArthurWynneGoldMedalispresentedtooneormoreindividualswhohave made a major contribution to biochemistry, molecular and cell biology inCanadaovertheircareer.Therecipientsofthislife-timeachievementawardtypicallyhaveattainedaninternationalprofileinresearch,haveplayedamajorroleinthedevelopmentandpromotionofthedisciplineinCanada,andhavealong-standingrecordof service to theacademiccommunity.TheMedal isnamed inhonourofProfessorArthurM.Wynne,thefirstPresidentoftheSociety,andwasinitiatedin2007tocelebratethe50thAnniversaryofCSMB.

Mona NemerChief Science Advisor, Ottawa

As Canada’s Chief Science Advisor, Dr.Mona Nemer’s main role is to advisethe Prime Minister and the Ministerof Science on science issues. Beforebecoming the Chief Science Advisor,she was Professor and Vice-President,Research, at the University of OttawaandDirectoroftheMolecularGeneticsand Cardiac Regeneration Laboratory.Dr. Nemer holds a Ph.D. in ChemistryfromMcGillUniversity.Priorto joiningthe University of Ottawa, she wasa Professor of Pharmacology at theUniversitédeMontréalanddirectedtheCardiacGeneticsUnit at theMontrealClinicalResearchInstitute.

Her research focussed on the heart,particularlyonthemechanismsofheartfailure and congenital heart diseases.She is the author of over 200 highlycitedpublicationsthathaveappearedin

prestigiousscientificjournals.Herworkhascontributedtothedevelopmentofdiagnostic tests for heart failure andthe genetics of cardiac birth defects.Shehastrainedover100studentsfromvariouscountries.

Dr. Nemer has served on severalnational and international advisorycommittees and executive boards,and is the recipient of many nationaland international honours. She is aMember of the Order of Canada, afellow of the Academy of Sciences ofthe Royal Society of Canada, a fellowof theAmericanAcademy of Arts andSciences,aKnightoftheOrdreNationalduQuébecandaKnightof theFrenchRepublic’s Ordre National du Mérite.She has also been awarded honorarydoctoratesfromFranceandFinland.

CSMB Arthur Wynne Gold Medal


Jim WoodgettLunenfeld-Tanenbaum Research Institute and the University of Toronto

Jim Woodgett is Director of theLunenfeld-Tanenbaum Research atSinaiHealthSystemandaProfessorintheDepartmentofMedicalBiophysics,Universityof Toronto.He receivedhisPh.D.inbiochemistryin1984fromtheUniversity of Dundee, Scotland withPhilip Cohen, and then pursued post-doctoral research at the Salk Institutewith Tony Hunter, where he workedfrom1984to1987onthebiochemicalandmoleculargeneticcharacterizationof protein kinases.He thenmoved toLondon, England to set up a researchgroupattheLudwigInstituteforCancerResearch at the Middlesex Hospital,where he isolated and characterizedthe genes for several key cellularregulatorsincludingGlycogenSynthaseKinase-3,ProteinKinaseB/AktandtheStress-ActivatedProteinKinases(JNKs).

In 1992, Dr. Woodgett moved tothe Ontario Cancer Institute inToronto, where his lab focussed onthe signal transduction mechanismsunderscoring malignant growth,degenerative diseases and diabetes.Healsoidentifiedpathwaysregulatingseveraltranscriptionfactors,generatedthefirstmousemodels for evaluationofGSK-3functions,andshowedthatitwas a physiological target of lithium.

In2005,hewasappointed the fourthdirector of the Samuel LunenfeldResearch Institute at Mount SinaiHospital, where he has continued hisworkonGSK-3,discoveredmechanismsto maintain the pluripotentiality ofstem cells, and studied themolecularetiologyofbreastcancer.

Of his 280 publications to date, overone third relate to GSK-3 and dateback to the last chapter of his Ph.D.thesis,highlightingthe longtime-linesassociatedwithpursuitoffundamentalbiological science. Over that time,he has trained over 40 students andfellowswhohavegoneontoevenmoreinterestingthingsaroundtheworld.

Dr.Woodgett is a Fellowof the RoyalSociety of Canada and has been aHoward Hughes Medical InstituteInternationalScholar,aswellasanMRCScientist andCIHR Senior Investigator.Morerecently,hehasplayedkeyrolesinCanadiansciencefunding,includingremediationofCIHR,andacommunitybuilder for support for the Naylorreport on fundamental science. He iscautiouslyoptimisticthe2018Federalbudget will begin to restore Canada’splaceinsupportofscientificresearch.


2017 Canadian Science Publishing Senior Investigator Award

Receptors and integrins interact with the cytoskeleton and the exoskeleton to initiate phagocytosis

Sergio GrinsteinProgram in Cell Biology, Hospital for Sick Children, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital and Department of Biochemistry, University of Toronto

Upon binding their cognate ligands, most receptorstransmit the information across the plasmamembraneby undergoing a conformational change. As a result,serpentine receptors stimulate heterotrimeric Gproteins, while a number of receptor tyrosine kinasesbecome activated and autophosphorylate, and alsophosphorylate cytosolic substrates. By contrast, certainimmunoreceptors become activated when clustered,formingoligomericcomplexes,withoutundergoingmajorconformationalalterations.Theseincludethephagocyticreceptors that mediate the elimination of pathogenicmicroorganisms and the clearance of apoptotic cellsanddebrisbytheinnateimmunesystem.Macrophages,neutrophilsanddendriticcellsexpressanassortmentofsuchphagocytic receptorswithvaried selectivity,whichenablestherecognitionofamultiplicityoftargets.

Clusteringofimmunoreceptorsiscausedbyexposuretomultivalenttargets; inthecaseofphagocyticreceptors,the prey displays on its surfacemultiple tightly spacedligands that force the aggregation of their receptors,bringing them sufficiently close to one another toinitiatesignalling.Howsuchclusteringresultsinreceptoractivation has been studied extensively, yet remainsincompletelyunderstood.ItisclearthatSrc-familykinases(SFKs)are involved intheearlieststagesoftheprocess,andthatthereceptorsthemselvesand/ortheirancillarysubunits bear tyrosine residues that are substrates for

phosphorylation by these kinases. However, whethertheSFKsareconstitutivelyactiveandwhether theyarephysicallyassociatedwiththereceptorsisstillthesubjectofdebate.Thepurposeofthisbriefreviewistosummarizerecent insights into the mechanism whereby innateimmune receptors coalesce, become phosphorylated,andtherebyinitiatethephagocyticresponse.

Receptor mobility amid a picket fenceMost of our studies of phagocytosis have used Fcg receptors(FcgR)asaparadigm.Fcg receptorsrecognizethe Fc (fragment crystallizable) constant region of IgG,which is exposed on the surface of antibody-coated (opsonized)targets.Tothebestofourknowledge,whenunstimulated, FcgR are not constitutively attached toany structural elements and, as such, are expected to diffusefreelyalongtheplasmamembrane. Contrarytothis prediction, however, we found that FcgR are partly confined(Freemanetal.,2018)anddiffusemuchmoreslowly than transmembrane proteins of comparablesize reconstituted into plain lipid bilayers (see Kusumiet al.,2012forexamples).Confinementwasdetectableby tracking single FcgR molecules using fluorescently- labelled Fab fragments of receptor-specific antibodies;imagingsinglereceptorsovertimerevealedthat,whilemobile,afractionofthemarerestrainedfromdiffusingfreelybyaphysicalbarrierakintoacorral.


Thattransmembraneproteinsareconstrainedbycorralswas first realized by Kusumi and his collaborators (e.g. Kusumi and Sako, 1996; Nakada et al., 2003); theseauthorsproposed that thedensemeshworkof corticalactinandassociatedproteinsthatunderliestheplasmamembranepresentsanobstacletofreediffusion,likelybycollidingwiththecytoplasmictailsofthetransmembraneproteins. Fences need to be supportedbypickets, andthe cytoskeletal fence is no exception. It requires firmattachment sites to remainassociatedwith theplasmamembrane,andtransmembraneproteinsarethoughttoserve this role. Suchpickets could in fact contribute tolimitthediffusionofmobilecomponentsintheplaneofthemembrane.Inthisregard,itisworthbearinginmindthat a substantial fraction of the plasmalemmal area(≈50%)isthoughttobeoccupiedbythetransmembranedomain of proteins; immobilization of a significantfractionofthesebytetheringtothecytoskeletonwouldgenerate impassable obstacles that would retard orevenpreventdiffusion.Thispredictionisconsistentwiththe observation that glycerophosphoinositide-linkedproteinsandevenexofaciallipidsdiffusemoreslowlyinbiologicalmembranesthantheydoinpurelipidbilayers(Kusumiet al.,2012).

Theprecedingconsiderationsimplythatmembranepicketsarenotonlyessentialtofastenthecytoskeletalmeshtothemembrane(therebycontributingtotheestablishmentof actin-based corrals), but are themselves importantdiffusionbarriers.Assuch, identifyingandcharacterizingthemisimportant.Remarkably,verylittleisknownaboutthe nature and properties of pickets. To address thisissue,wepostulated thatbonafidepicketsshouldmeettwominimalcriteria:1)theymustbeintegralmembraneproteins that associate (at least transiently) with thecortical cytoskeleton and 2) to have significant impacton the diffusion of mobile components, they must bereasonablyabundant.Applyingthesecriteria,weselectedCD44as a likely candidate. This transmembraneproteinwasknowntolinktoactinfilamentsviaezrinandankyrin/spectrin(Fehonet al.,2010),andwasreadilydetectableby immunostaining in phagocytic cells, suggesting itis abundant. We used specific antibodies to quantifyCD44 in macrophages and established that there areapproximately106copiesofthisproteinpercell(Freemanet al., 2018), a comparatively largenumber.Havingmetthetwocriteriatofunctionasapicket,weproceededtotest whether CD44 does in fact curtail the diffusion ofmobiletransmembraneproteins,suchasFcgR.Tothisend

weusedtwoindependentapproaches:depletionofCD44usingsiRNA,andalsocomparisonofwildtypeandCD44-

/- macrophages. We found that reducing or eliminatingCD44improvedthemobilityofFcgR,validatingtheroleofCD44asdiffusion-limitingpicket.

Collectively, theseobservations imply thatareasof themembrane that are rich in cytoskeletal-anchoredCD44will confine receptors and thereby limit their ability tocluster and become activated. This raises the questionofwhetherCD44isfirmlyandhomogeneouslyanchoredthroughoutthecell.Inthiscontext,itisworthbearinginmindthat,asimmunesentinels,macrophagesconstantlymigrate to survey their environment. During thisexploratorysurveillancethecellspolarize,withaleadingedge characterized by a broad lamellipodium and anarrowertrailingedgeoruropod.Asdescribedearlierforlymphoidcells,wefoundthattheuropodofmacrophagesis rich in ezrin, which is comparatively depleted fromthe lamellipod. If ezrin is indeed responsible for CD44tethering to the cytoskeleton, immobile pickets shouldbemoreabundant in the trailingedgeof the cell. Thispredictionwasvalidatedexperimentally:weusedsingle-moleculetrackingtoassessthemobilityofCD44atthefrontandbackofindividual,polarizedmacrophages.OurresultsclearlyindicatedthatCD44isconsiderablymoremobileinthelamellipodthanintheuropod.Moreover,aspredictedbasedonthedifferentialdegreeoftetheringofthepicket(s),themobilityofFcgRwasalsogreateratthefrontofthecells(Figure1).Thesedifferencesarenotattributable todisparities in thenetamountofF-actin,which seems to be similarly dense in the lamellipodand uropod. Instead, we believe that the manner inwhich the actin is organized is key:much of the actindriving theextensionof the lamellipod isnucleatedbyArp2/3,whichgeneratesbranchedfilaments that growperpendicularly to the plane of the plasmalemma. Bycontrast,intheuropodforminsseemtocontributemoreto the formation of F-actin filaments, which are linear(unbranched)andtendtorunclosetoandparalleltothemembranebilayer(Figure1).

These observations have important functionalimplications.Phagocytosiswillproceedmoreefficientlyat the leading edge of the migrating cells (Figure 1),where the macrophages are most likely to encounterpreyastheymoveupthegradientofchemoattractantsreleased by the pathogens themselves, or by the cellsthatareinflamedduringinjuryorinfection.


CD44 is not an ordinary picket. In addition to itstransmembrane and cytoskeletal-binding intracellularregions, it has a unique extracellular region bearing aLink(alsocalledXLink,forextracellularLink)domainthatserves as a receptor for hyaluronic acid (hyaluronan).Hyaluronan is a long, unbranched glycosaminoglycanconsistingofabasicunit,aheterodimerofD-glucuronicand N-acetyl-D-glucosamine linked via alternatingβ-(1→4)andβ-(1→3)glycosidicbonds,thatisrepeatedhundreds or even thousands of times, forming strandsofextraordinary lengththatcanreachseveralmicrons!The inordinate length of the hyaluronan polymer,together with the high density of receptors (CD44)on themembrane, result in thefirmadherenceof theglycosaminoglycanto thecell surface.Theprofusionof

hyaluronanstrands,alongwithits immobility,createsarelativelyrigidmeshontheoutersurfaceofthecells,insomewaysakintotheinnercytoskeletalmeshwork.

Like the cortical cytoskeleton, the hyaluronanglycocalyx can interfere with the lateral displacementof membrane-associated molecules, particularly thosethat extend considerably into the extracellular space.Moreover, the anionic glycocalyx layerwill impede theaccess of particulate material, especially that which isnegativelycharged,tothe(relativelyshort) phagocyticreceptors. One can therefore predict that treatmentof the macrophages with hyaluronidase or with otherglycocalyx-removing enzymes will in fact facilitatephagocytosis, and that access of phagocytic targets

Figure 1. Schematic diagram illustrating the role of the actin cytoskeleton in phagocytic receptor mobility and function.Atthefrontofamigratingphagocyte,F-actinisprimarilypolymerizedbyArp2/3,whichpropelstheextensionofthelamellipodium.Thisformofbranchedactin,whichgrowsperpendiculartotheplaneofthemembrane,isconducivetophagocyticreceptormobility,whichfacilitatesengagementofthepreyandreceptorclusteringandactivation.SeveringoffilamentsbycofilinprovidesmonomericactintotheArp2/3complex.Atthebackofthecell(theuropod)actinismainlypolymerizedbyformins,whicharestimulatedbyRhoAandCdc42andgeneratelinearactinfilamentsthatrunparalleltotheplaneofthemembrane.Suchfilamentsarepreferredbyezrin,whichbridgesCD44andotherpicketsto theactinmeshwork, thereby confiningand reducing themobility of phagocytic receptors.Asa result, receptorclusteringandactivationareminimized.


Figure 2. Schematic diagram illustrating the generation of a diffusion barrier during activation of phagocytic receptors.Engagement of phagocytic receptors (e.g. FcγR; showningreyunderthetarget)inducesinside-outactivationofvicinal integrins (shown as heterodimers in violet). Thecloseappositionofintegrinsandreceptorstothetarget(showningreen)formsadiffusionalbarrierthatexcludesthe longer and rigid phosphatases CD45 and CD148(shownoutside thephagocyticcup, inbluewithyellowsugar residues). Outside the cup, the phosphatasesaid inpriming theSrc-familykinases (SFKs),while theirexclusion from the area of the cup enables sustainedactivationoftheSFKs.

wouldbegreaterat the frontofmigratingcells,wherethepicketsthatanchortheexoskeletonaremoremobile,thanatthecell’sback.

Initiation and spreading of receptor signalsIt is generally acknowledged that, once theimmunoreceptors are clustered, the next step involvestheactivationofSFKs.SFKsexistinthreefunctionalstates:inhibited, primed and activated. Phosphorylation of atyrosineresiduelocatedneartheC-terminusinhibitstheactivityofthekinase(DavisandvanderMerwe,2006).This results from a conformational change associatedwith the intramolecular association of the C-terminalphosphotyrosinewiththeSH2domainofthekinase.Thisinhibition can be relieved by CD45 and/or CD148, tworelatedtyrosinephosphatasesthatareuniquelyabundantinhemopoieticcells.Dephosphorylationoftheinhibitorytyrosine primes the SFKs for activation,which requiresthe additional phosphorylation of another tyrosineresidue,locatedfurtherawayfromtheC-terminus.ThisphosphorylationcanbeenactedbytheSFKsthemselvesorbyanotherimportanttyrosinekinase,Syk.

Itisimportanttonotethattheactivatingphosphotyrosineis also a substrate of dephosphorylation by CD45and CD148. How then is the activation of the kinasesestablishedandmaintained?Thesecretliesinthephysicalsegregation of the CD45/CD148 from the activated(phosphorylated) kinases. This striking phenomenonwasfirstobservedbyGoodridgeet al.(2011),whonotedthe marked exclusion of the phosphatases from sites

where phagocytosis was being initiated (i.e. nascentphagosomal cups). The process whereby CD45 andCD148areexcludedfromthecupisasinterestingasitisremarkable.Thephosphatasesaredisplacedvectorially(radially)awayfromthesiteswherephagocyticreceptorsare engaged by ligands on the particle. Despite thenet directional (vectorial) displacement – which canamounttoseveralmicrons–theindividualphosphatasemolecules appear to be driven by Brownian motion,aswe validatedby single-particle tracking (Freemanet al.,2016).Whatconfersdirectionality to theprocess istheconcertedformationandevolutionofanexpandingdiffusionbarrierthatexcludesCD45andCD148fromtheareaswherethephagocytemakescontactwithitstarget.The tight apposition of the two interacting surfacesextrudesthephosphatases,whicharetoolongandrigidtofitintheconfinedspaceofthecontactzone(Figure2).

While binding of the comparatively short phagocyticreceptorstotheirligandsonthetargetsurfacemayappeartobesufficienttoexcludeCD45/CD148,theleadingedgeofthediffusionbarrier(andhenceoftheexclusionzone)isinfactestablishedbyintegrins(Figure2),whichgeneratepodosome-likestructuresaheadofthereceptorcontactregions.The integrinsareactivatedfromthe insideoutby signals emanating from the stimulated phagocyticreceptors. This has two important consequences: 1) itextends the reach of the contact zone to areaswhereFcγR-IgGinteractionshavenotyetoccurred(andmaynotbeabletooccur, if the liganddensity is low,as is likely


tobethecaseunderphysiologicalcircumstanceswherethe supply of immunoreactive IgG is limited), and2) itenables themore promiscuous integrins to secure theassociationwiththepreyandpossiblydrawdistantIgGmolecules near additional receptors on the phagocytesurface. How the expansion of the diffusion barrier iscoordinatedremainstobeestablishedindetailandisthesubjectofcurrentstudiesinourlaboratory.

In closing, I hope that this brief summary of recentwork in our laboratory illustrates how a seeminglysimple interaction between phagocytic receptors andtheir ligands, heretofore thought to operate merelyas “molecular velcro”, is considerably more subtleand complex, encapsulating interactions between thereceptorsandahighlystructuredyetdynamiccytoskeletalpicketfence,anunderappreciatedexoskeletongeneratedby the glycocalyx, and integrins, all interconnected bycarefullyorchestratedsignaltransduction.

AcknowledgmentsI would like to thank Dr. Spencer Freeman forgeneratingmostofthedatadiscussedinthisreviewand for his help drafting the figures. Original workin the author’s laboratory is supported by grantFDN-143202 from theCanadian Institutes ofHealthResearch.

References

Davis,S.J.,andvanderMerwe,P.A.(2006).Thekinetic-segregationmodel: TCR triggering and beyond.Nature Immunol7,803-809.

Fehon,R.G.,McClatchey,A.I., andBretscher,A. (2010).Organizing the cell cortex: the role of ERM proteins.NatureRevMolCellBiol11,276-287.

Freeman, S.A., Goyette, J., Furuya, W., Woods, E.C.,Bertozzi, C.R., Bergmeier,W.,Hinz, B., van derMerwe,P.A., Das, R., and Grinstein S. (2016): Integrins forman expanding diffusional barrier that coordinatesphagocytosis.Cell,164:128-140.

Freeman,S.A.,Vega, A.,Riedl, M., Collins, R.F.,Ostrowski,P.P., Woods, E.C., Bertozzi, C.R., Tammi, M.I., Lidke,D.S., Johnson, P.,Mayor, S., Jaqaman, K., andGrinstein,

S. (2018): Transmembrane pickets connect cyto- andpericellular-skeletons forming barriers to receptorengagement.Cell,172:305-317.

Goodridge, H.S., Reyes, C.N., Becker, C.A., Katsumoto,T.R., Ma, J., Wolf, A.J., Bose, N., Chan, A.S., Magee,A.S., Danielson, M.E., et al. (2011): Activation of theinnate immune receptor Dectin-1 upon formation of a‘phagocyticsynapse’.Nature,472:471-475.

Kusumi,A.,Fujiwara,T.K.,Chadda,R.,Xie,M.,Tsunoyama,T.A., Kalay, Z., Kasai, R.S., and Suzuki, K.G. (2012).Dynamicorganizingprinciplesoftheplasmamembranethat regulate signal transduction: commemorating thefortiethanniversaryofSingerandNicolson’sfluid-mosaicmodel.AnnuRevCellDevBiol28,215-250.

Kusumi,A.,andSako,Y.(1996).Cellsurfaceorganizationby themembrane skeleton.CurrOpin Cell Biol 8, 566-574.

Nakada, C., Ritchie, K., Oba, Y., Nakamura, M., Hotta,Y., Iino, R., Kasai, R.S., Yamaguchi, K., Fujiwara, T., andKusumi, A. (2003). Accumulation of anchored proteinsforms membrane diffusion barriers during neuronalpolarization.NatureCellBiol5,626-632.


2017 CSMB New Investigator Award

Structural insight into nonribosomal peptide synthetases, natural antibiotic factories

Martin SchmeingDepartment of Biochemistry, McGill University

Introduction to nonribosomal peptide synthetases and their productsAll members of the Canadian Society of MolecularBiosciences are familiar with the ribosome, but notall know that there are other massive peptide-makingmolecular machines in nature. In bacteria and fungi,there is a class of megaenzymes called nonribosomalpeptide synthetases (NRPSs) (1,2). Instead of makingproteins, NRPS make a wide variety of short peptidesecondarymetabolites (3). Forexample,NRPSproductsinclude antibacterials, antifungals, antivirals, anti-tumours,immunosuppressants,siderophores,toxinsandvirulence factors. Some of these NRPS products are ofcritical importance to human health, from themillionsof lives penicillin has saved, to the organ transplantsmade possible by cyclosporin and related compounds,to fighting methicillin-resistant Staphylococcus aureus infectionswithcelophalosporin,andcounteringhospitalGram-positiveinfectionswithdaptomycin.

NRPS products often don’t resemble proteinaceouspeptides.Aswellasthe20standardaminoacids,over500others can be incorporated into the peptide, includingD-amino acids, non-proteinaceous amino-acids, cyclicamino acids, N-, O- and C-methylated amino acids,hydroxylatedaminoacids,arylacids,hydroxy-acids,ketoacids and fatty acids (4,5). The peptide products arealsooftencyclicandcanbebranched(Figure1A).ThesedifferencesfromproteinaceouspeptidesresultfromthedissimilarmechanismsofreactionandprocessivityoftheribosomeandNRPSs.

NRPSs resemble assembly lines that are dedicated tomaking one kind of peptide (6). They are organizedintomodulesof >1000aminoacids,witheachmodulepossessingthecatalyticactivitiesrequiredfortheadditionof one specific amino acid or othermonomer buildingblock into the growing peptide (1,2,7,8). Typically, thenumber and order of the modules correspond to thelength and sequence of amino acids in the peptideproduct. NRPSs can be as short as one module or aslarge as eighteenmodules,with amolecularweightofover2MDainasingleproteinchain.Theycanbeasinglehugepolypeptidechainorbesplitovermultiplechainswhich assemble through non-covalent interactions (9).Modulescontainmultipledomains,eachwithaspecificfunctioninpeptidesynthesis.Abasicmodulecontainsacondensation(C)domain,anadenylation(A)domainandapeptidylcarrierprotein(PCP)domain.

Figure1BoutlinesthecatalyticcycleinacanonicalNRPSelongation module, which can be thought of as onegroupofstationsontheassemblyline(1).TheAdomainrecognizesandbindsthesubstrateaminoacidandfirstcatalyzes itsadenylation, then its linkageasa thioesterto the prosthetic 4’-phosphopantetheinyl moiety ona PCP domain. The PCP domain transports the aminoacylthioestertotheCdomain.TheCdomaincatalyzescondensation (peptide bond formation) between thisaminoacyl-PCPandanaminoacidorpeptideattachedtothePCPdomainoftheprecedingmodule.Thistransfercreatesanelongatedpeptidyl-PCP,whichthenmovestothedownstreamCdomain forpeptidedonation in the


next condensation reaction. Once a PCP domain hasdonateditsattachedpeptide, it isfreetoacceptanewaminoacidfromtheAdomainandparticipateinthenextcycleofassemblylinepeptidesynthesis.

NRPSsusuallydon’tjustconsistofmultiplecopiesofthesethreekindsofdomains,however.InalmostallNRPSs,oneormoremodulescontainadditional“tailoring”domains,domainswhichintroducechemicalmodificationintothepeptideco-synthetically(10,11).Thesetailoringdomainsinclude: epimerisation (E) domains,which catalyze theracemization of L to D amino acids; methyltransferasedomains, which conjugate methyl groups to carbons,oxygensornitrogensinthepeptide;cyclizationdomains,whichreplaceCdomainsandcatalyzebothcondensationand intramolecular heterocyclization; reductase andoxidase domains which introduce or remove doublebonds,andformylation(F)domains,whichN-formylatethefirstaminoacid(5).TerminationmodulesalsomustcontainadedicateddomaintoreleasethepeptidefromitscovalentattachmenttothePCPdomainintheappropriateform. The last domain in anNRPS terminationmodule

is often a thioesterase (TE) domain, which cleaves offcovalentlytetheredpeptidebycatalyzingattackofwater(resultinginalinearproduct)oraninternalnucleophile(givingacyclicproduct)(12).OtherNRPSsterminatewithreductase(R)domains,whichperformreductivecleavageofthepeptidethioestertoanaldehydeoralcohol(13).The general organization of a canonical NRPS is thus A-PCP-(C-A-PCP)n-TE/R, with the tailoring domainssometimes inserted. The combination of the >500possible building blocks, many tailoring domains andseveralmodesof peptide release allowNRPSproductstooccupyavastlylargerportionofchemicalspacethanwouldbeexpectedforsmallpeptides(4,10,11).

As described, canonical NRPSs have a straight-forwardsynthetic logic, with each core and tailoring domainperforming a known role. In addition, the selectionof the amino acid/monomer substrate is determinedby a binding pocket which has been so well studiedthat it can now be predicted robustly from A domainsequence refinements (14-17). Together, this makesNRPSs remarkable in that theirmetaboliteproductcan

Figure 1. NRPS products and synthetic cycleA,Somenonribosomalpeptides;B,ThesyntheticcycleofabasicNRPSelongationmodule.FigureadaptedfromReimeretal.(24).


be predicted fairly confidently from simple sequenceanalysesofthedomainspresentineachmodule,andtheinferredspecificityofeachAdomain.

Becauseofthesimplesynthetic logicofNRPSsandthetherapeuticorcommercialvalueoftheirproducts,therehas been great excitement about their potential as asource of new bioactive compounds. Bioengineeringstrategies for NRPS are conceptually straightforward:Changingthesubstratespecificityofmodules,reorderingmodules,and insertingorremoving individualdomainsall have predictable effects on the peptide product.Furthermore, combinatorially ordering modules couldproduce vast libraries of diverse peptides. Efforts toexploitthesesystemshavebeenunderwayfordecades,buthaveonlyhadlimitedsuccess(18-23).Thepotentialofcombinatorialorrationalbioengineeringmethodscanbefacilitatedbyadeepunderstandingofthearchitectureandmechanismsofthesehugemachines.Manyexcellentstructural studies have contributed to our currentunderstandingoftheNRPSs.Essentiallyallthecoreandtailoring domains have been structurally characterized,there are several nice di-domain structures, and a fewmodules have been determined (reviewed in (7,24)).However,more studiesondomainarchitectures, large-scale motions and domain-domain interactions arenecessarytounderstandthesemegaenzymes.

Linear gramicidin synthetaseMost of the research presented at the CSMB NewInvestigator Award lecture focussed on an interestingNRPScalledlineargramicidinsynthetase,whichmakesaclinically-usedtopicalantibiotic(25,26).Lineargramicidinis part of the Polysporin eye drops and triple actionantibioticcocktailsthatmanyCSMBmemberswillhavein theirmedicine cabinet. Linear gramicidin synthetaseisa16-modulesystem,spreadover4proteins(LgrA-D)thatcometogetherthroughnon-covalentinteractions.ItwasfirstdescribedbyMarahielandco-workersaroundadecadeago, andhas twonotable featureswhichareimportant for the peptide product (27,28). First, everysecondmoduleinthesystemcontainsanepimerizationdomain, and thus every second residue in lineargramicidinhasDchirality.(LineargramicidinisFormylVal-Gly-Ala-D-Leu-Ala-D-Val-Val-D-Val-Trp-D-Leu-Trp-D-Leu-Trp-D-Leu-Trp-Ethanolamine.)Thisallowsthepeptidetofoldintoanunusual“beta-helical”conformation,wherethemainchainisinthecentreofthebroadhelixandthesidechainsarefacingoutward.Second,thefirstdomaininthe

initiationmoduleof theNRPS isa formylationdomain,whichcatalyzesN-formylationofthefirstresidue,valine.The formyl group allows head-to-head dimerization oflinear gramicidin. Two gramicidin helices are just theright size to span abacterialmembrane, insertion intowhichispromotedbythepeptide’snon-polarsidechains(26).Thecentreofthebetahelixiswideenoughtoallowmonovalentionstopassfreelythroughthemembrane,allowing linear gramicidin to form a pore, collapse theiongradientandkillthebacteria.

We set out to gain a structural understanding offormylationinNRPSs(25).Marahielhadestablishedthatthe formylation (F) domainwas homologous to stand-alone formyl transferase proteins, and that it actedafter adenylation and ligation of valine to the thiol ofthePCPdomain’sphosphopantetheinearm(thiolation),but before peptide donation in the second module’scondensationdomain.Ourspecificquestionswere:WhatisthestructureoftheFdomain?Istheformylationeventthesameasincanonicalformyltransferaseproteins?HowistheFdomainincorporatedintotheNRPSarchitecture?Whatareitsorigins?HowdoesthePCPdomaininteractwithanddeliverthesubstratetotheFdomain?

Our first experiments were quite modest in scope. WewantedtosolvethestructureofaconstructofLgrAthatonlycontainedtheFdomain.Thetwotalentedgraduatestudents who started working on this project, JaniceReimer andMartin Aloise, had each been focussing onother NRPS projects that were, despite their excellentefforts, not yielding many results. We believed that aconstruct of a ~180 residue domain, which displayedhomology to previously characterized proteins, may beeasily amenable to structural study. (And if the larger,more interestingconstructsofLgrAwereproblematictoworkwith,thestudiesontheFdomainalonewouldgiveJaniceandMartintheirfirstpaperfromthelab,allowingthemtoreturntotheirmainprojectswithapublicationintow.)JaniceandMartinclonedandattemptedexpression,purificationandcrystallizationofFdomainconstructsfromseveralspecies,buttheseconstructsprovedproblematic.Theconstructsexpressedonlyat low levels,wereproneto aggregation and never crystallized. However, theprojecttookaturnforthebetterwhenweswitchedtoF-Adidomainconstructs.

Linear gramicidin synthetase F-A didomain fromBrevibacillus parabrevis expressed at moderate levels,behaved well during purification and readily formed


crystals, thebestofwhichdiffracted to2.5Å resolution(25). Marahiel had established that the formylation (F)domainwashomologoustostand-aloneformyltransferaseproteins (27). We solved the structure by molecularreplacement, which revealed a very elongated F-A di-domain conformation. The F domain was recognizablebecause of its expected similarity to formyltransferaseproteinsandtheAdomainlookedlikeacanonicalAdomain(29).Theirfusionproducedafairlylargeinterfacebetweentheendsofeachdomain,whichburies830 Å2ofsurfacearea, and gives the appearance that the F domain was“snappedon”likeaLegoblocktotheNterminusoftheAdomain.TheextensiveinterfaceisreminiscentofinterfacesbetweenCdomainsandAdomainswithinanelongationmodule,whichisalsolarge,butverydifferentfromothertailoring domains, for example the E domain, which isconnectedtotherestofitsmoduleonlybyaflexiblelinker.This interfacehintedthatitwasafortuitousgenefusioneventthat ledtotheincorporationoftheFdomainintotheNRPSarchitecture in this elegantway. Furthermore,structural and sequence analyses showed that the pre-transfergenelikelyencodedaformyltransferaseinvolvedinmodificationofsugar-nucleotidesubstrates(25).

TheF-Adidomain structure revealedhow theFdomainwas incorporated into NRPS architecture, but becauseof the absenceof thePCPdomain (anddisorder of theimportant C-terminal part of the A domain called theAsub), itdidnotshowhowtheFdomainfunctionsinthe

LgrA initiation cycle. So, Janice andMartin expressed afullinitiationmodule(F-A-PCP)construct,treatedsampleswithseveraldifferentcocktailsofsubstratesandinhibitors,and undertook crystallization (30). This full initiationmodulealsogaveseveralinitialcrystallization“hits”,threeofwhichcouldbeoptimizedforstructuredeterminationatbetween2.6Åand3.8Åresolution(Figure2).

Thepositionof theAsub andPCPdomainvariedbetweenstructures,butineach,theextendedF-Acoreconformationwasmaintainedinaverysimilarway.Thatthisconformationwasmaintainedinmanydifferentcrystalpackingenvironmentshintedthattheextendedconformationisaconstant,buttotestthisweturnedtosolutionsmallangleX-rayscattering(SAXS). The low-resolution envelope calculated fromthe scattering curve fittedwell with one crystallographicconformationofF-A-PCP,butnotsurprisingly,nosimulatedscatteringcurvefromasinglecrystallographicconformationfullyrecapitulatedtheexperimentaldata.However,whenasingleextendedF-Acoreconformationwascombinedwiththe ensemble of positions of Asub and PCP domain, thesimulatedscatteringcurvematchedtheexperimentaldataexceedinglywell. TheSAXSdata is thus consistentwithaconstant elongated F-Acore conformation and mobility ofsmallerelements.TheactivesitesoftheFandAdomainsare>50Åapart in theelongatedconformationandmustthereforeremain farapart throughout thecatalyticcycle,despitecatalyzingsuccessivereactions.Gratifyingly,throughappropriateuseof substrates and inhibitors, butwithno

Figure 2. Synthetic cycle of the initiation module of linear gramicidin synthetase A.A,Schematicoftheinitiationcycle.B,Crystalstructuresoftheinitiationcycle.FigureadaptedfromReimeretal.(24)andReimeretal.(25).Pleaseseealsotheanimationatwww.youtube.com/watch?v=0Gge2uSvZ1U&feature=youtu.be.


smallcontributionofgoodfortune,ourF-A-PCPstructurescaptured each major catalytic stage of the initiationmodule’ssyntheticcycle.Severalofthestatesrecapitulatedthoseseenincatalytically-relevantstructuresofAorA-PCPconstructs,butthetailoringstoryisnew,andallthesestatesareseeninthecontextofasingleproteinforthefirsttime(Figure2)(29,31-33).

ThecyclestartswithvalineandATPbindingtotheAdomaininan“open”conformation,wheretheAsubisrotatedbacktogiveaccesstothebindingsites(Figure2)(34).TheAsub then rotates “closed”,donatinga lysine to facilitate theadenylationreaction(29,35).Thisvalineadenylateisthesubstrate in thenextstep, thiolation, forwhich theAsub rotates140°,allowingthePCPdomaintobindandaccepttheaminoacidasathioesteronitspantethienemoiety(36,37).Next,thevalinylthioestermusttravelthe>50ÅtotheFdomain,whichrequires large-scalemovementsof both the Asub and the PCP domain. The Asub rotatesfully180°andtranslocatesitscentreofmassby21 Åtofacilitatethe75°rotationand61 ÅtranslocationthePCPdomainundergoestodeliverthevalinylthioestertotheformylation active site. There it accepts a formyl grouponto its amino group fromN10-formyl tetrahydrofolateby a canonical formyl transfer mechanism (27,38,39).The PCP then must make another massive movementto donate the formyl-valinyl in the peptidyl transferasereactionintheCdomainofthedownstreammodule(forwhichnostructureispublished,butatwhichtheCSMBaudience got a sneak peek). Donation of the formyl-valinyl group frees the PCP domain to participate inthe next round of assembly-line synthesis. A simplifiedversion of the synthetic cycle in “morphing” animationformwaspresented,andcanbeviewedatwww.youtube.com/watch?v=0Gge2uSvZ1U&feature=youtu.be.

Themost informative single structure of the series wesolvedisthatofF-A-PCPintheformylationstate(Figure2).Inthisstructure,thePCPdomainpresentsthevalinyl-pantetheinetotheFdomain’sactivesite.ThePCPdomainmakesasmallcontactsurfacewiththeC-terminalportionoftheFdomain,andisattherightdistanceforthevalinyl-pantetheinetostretchouttothecatalytictriadandfTHFcofactor. (The 3.8 Å resolution of this structure meantthe valinyl-pantetheine was not visible in the electrondensity,butaconformationwhichpositionedthevalineamino group perfectly for reaction could be easilymodelled.) Superimpositionof the F-A-PCP formylationstatewithasugar-nucleotideformyltransferaseshowed

that the valinyl-pantetheine and the sugar-nucleotidesubstrate bind in very similar ways, and share similarphysical lengths and mixed hydrophilic/hydrophobicnature (38). This cryptic similarity between substrateslikely allowed the nascent F domain to quickly evolveactivityonNRPSsubstrates.

A comparison of the F-A-PCP formylation state withformyl-methionyl transferase (FMT) is also informative.Inbothenzymes,themacromolecularsubstrate(valinyl-pantetheine-PCPandMet-tRNAfMet)makerelativelylittlecontact with the catalytic formylation domain. In FMT,there is a second, C-terminal domain whose role is tomakeextensivecontactswiththetRNA,positioningitforformylation (40). In an analogous fashion, we observetheAsub forminganovel, second interfacewith thePCPdomain, which appears to aid in positioning its valinesubstrateforformylationintheFdomain.

More than a moduleThestudiesoftheinitiationmoduleofLgrAshowaniceholistic picture of the synthetic cycle within amodule.The publication describing these appeared adjacent toa very nice one from the Gulick laboratory describingstructures of elongation modules (41). However, thequestionofwhatNRPSswithmorethanonemodulelooklikeisstillanopenone.Ithasbeenproposedthatmulti-modularNRPSsassumea super-helical structurewithaconstantpitch.MikeTarryandAsfarulHaquefromthelabperformedastudywithacanonical,non-tailoringNRPStostarttolookatsuper-modulararchitecture(42).

The bacillibactin synthetase protein DhbF was chosenforthisstudylargelybecauseofitscanonicalC1-A1-PCP1-C2-A2-PCP2 architecture (31,43-45). We took a double-pronged approach of electron microscopy and X-raycrystallography.Inourcrystallographywork,becausewewereunabletocrystallizethefulldimodularconstruct,wetargetedaconstructofthe3rdto5thdomains,A1-PCP1-C2. Wereasoned that since this construct contains the lastlarge domain from the first module and the first largedomainfromthesecondmodule,itcouldrevealinsightfulinformation about the relative orientations of the twomodules.Weusedanaminoacyl-vinylsulfonateadenosinedeadend inhibitor,whichbecomesattachedtothePCPandlimitsitsmovements,whichfacilitatedcrystallizationand structure determination to 3.0 Å resolution(37,41,42,46-48). TheA andPCPdomainsofA1-PCP1-C2 were in a conformation similar to the thiolation state,as expectedwith use of the dead-end inhibitor (Figure


3). Surprisingly, therewere no interactions between A1 andC2.TheonlycontactbetweenC2andtherestoftheprotein isbetweenitsdonorsiteandthe“backend”ofPCP1. This contact cannot be maintained throughouta productive synthetic cycle, hinting that there is not aconstant module:module interface. The negative stainEMof full dimodularC1-A1-PCP1-C2-A2-PCP2 lent supporttothisnotion.Fromasingledataset,inhibitedwiththesamekindofdeadendinhibitors,wecouldcalculate5(ormore)differentmolecularenvelopes,allofwhichcouldbefitted todidomainmodelswithdifferent conformationsandmodule:module interfaces. Thus, even when DhbFwas restricted to a single catalytic state by dead-endinhibitors, it still displayed a large number of super-modular conformations. It is possible that otherNRPSsmayassumearegular,helicalconformationofmodules,butitdoesnotappearthatDhbFdoes(42).

Together, the CSMB award lecture is a story ofconformationalchanges.WithLgrA,wesawthatthemaintwodomainsarelargelyrelativelyfixed,butthatAsubandthePCPdomainmustbedynamictoperformasyntheticcycle.ThestudieswithDhbFshowedthatvaryingmodule:moduleconformationsarealsoprevalent.Therearecertainlylikelytobeotherimportantconformationstobecapturedinthefuturebeforewehaveacompleteviewofthesecomplicatedandelegantmacromolecularmachines.

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News from Member Departments

Dalhousie UniversityDepartment of Biochemistry and Molecular BiologyCorrespondent: Stephen L. Bearne

The2017-18academicyearhasbeenaninterestingyearfortheDepartmentofBiochemistryandMolecularBiologyatDalhousieUniversity.Withanewstrategicplanwithinthe Faculty ofMedicine, research has been prioritizedinto “waves” that could impact future recruitmentsand research directions for the Department. Stephen BearnewasrenewedasHeadforasecond5-yearterm.John ArchibaldwasappointedDirectoroftheCentreforComparativeGenomicsandEvolutionaryBioinformatics,replacing Andrew Roger who had served in that rolefor 9 years since the Centre’s inception in 2008. FordDoolittlewasawardedthe2017MotooKimuraLifetimeContributionAwardfromtheSocietyforMolecularBiologyand Evolution.Paola Marignani hostedDr. Feng Zhang(MIT,noted forhisworkonoptogeneticsandCRISPER)who, as the Dalhousie Medical Research Foundation/Gairdner Lecturer, delivered a comprehensive seminarto a packed auditorium. The Department’s laboratorytechnicianHeidi MacKinnon receivedthe2017FacultyofMedicineExcellenceinLeadershipAwardinrecognitionof the vital role that she plays in the operation of theDepartmentanditsundergraduatelaboratories.

The graduate students and post-doctoral fellowsorganized a student research day that featured posterpresentations, brief lectures from various faculty ontheir career paths, and a seminar by Dr. Anne Spang(University of Basal). In addition, the Department hascontinuedtocelebratethesuccessofitsstudents,post-

doctoral fellows, and research associates during the pastyear. Mitesh Nagar, a graduate student with Stephen BearnewasawardedthePatrickPrizeforbestPhDthesis.Dr. Lingling Xu, a post-doctoral fellowwith Jan Rainey and Paul Liu, and Sergio Muñoz-Gómez, a graduatestudentwithClaudio SlamovitsandAndrew RogerbothreceivedBethGourleyConferenceAwards,whichwereestablished byCatherine Lazier and her husband JohnLazier.

Our alumni (and anyone else interested) are invitedto find out about the latest news and events of theDepartment of Biochemistry & Molecular Biology athttp://www.biochem.dal.ca.

Dr.JohnArchibald,newDirectorofDalhousie’sCentreforComparativeGenomicsandEvolutionaryBioinformatics(photocourtesyofHeidiMacKinnon)

DeanDavidAndersonpresentsHeidiMacKinnonwiththe2017FacultyofMedicineExcellencein Leadership Award (photocourtesyofHeidiMacKinnon)

Dr.CatherineLazierpresentstheBethGourleyConferenceAwardtoDr.LinglingXu(PDF)(photocourtesyofHeidiMacKinnon)

Dr.CatherineLazierpresents the Beth GourleyConferenceAwardtoSergioMuñoz-Gómez(Ph.D.student)(photocourtesyofHeidiMacKinnon)


Hospital for Sick Children Research Institute, TorontoCorrespondents:CharlesDeberandPeterKim

Cell Biology Program

CIHR Early Career Investigator in Maternal, Reproductive, Child and Youth Health:

Dr. Vito Mennella, Scientist,Hospital for Sick Children,and Assistant Professor,Department of Biochemistry,UniversityofToronto,wasoneof the ten recipients of theCIHREarlyCareerInvestigatorin Maternal, Reproductive,Child and Youth Health. Dr.Mennella was awarded thegrant in the circulatory andrespiratorysectionforhiswork

onthediscoveryofcommondiseasemechanismsfoundinsensory andmotile ciliopathies. Dr.Mennella is an earlycareer investigatorwhose research focusses on revealingmechanisms of rare diseases caused by centrosome andciliaproteinsusingadvancedimagingmethods.

2017wastheyearfornewinfrastructuresforCellBiologyand SickKids.Drs. Daniela Rotin, Michael Moran, andJohn BrumellwereeachawardedCanadaFoundationforInnovationgrantstoestablishthreemajorinfrastructuresat theHospital forSickChildren.Dr.Rotin’sapplicationtitled “3D-ORG: 3D screening infrastructure for tissueORGanoids and model ORGanisms” will bring cutting-edge high-content and high-throughput drug andphenotypic screens in organoids, tumorspheres, andsmallorganismssuchasworms,zebrafishembryosandflyembryos.Dr.MichaelMoran’sawardwillbringstateoftheartMassSpectrometrytoidentifydisease-associatedproteinsinpatientsamples.BothinfrastructureswillbehousedintheSPARCBioCentrefacilityatSickKids(http://lab.research.sickkids.ca/sparc/).Dr.JohnBrumell’sawardwillbringthelatesttechnologyin3Delectronmicroscopyimaging.ThecombinationofaSerialBlock-Facescanningelectron microscope and a Focus Ion Beam electronmicroscope will allow researchers to rapidly acquire3-dimensionalEMimagesassmallasacellandaslargeas an entire C. elegans. Combined with other existinginfrastructures at SickKids, this new equipment will

provideresearchersinToronto,andtherestofCanada,withnoveltoolstoaddressunmetbiologicalquestions.

Molecular Medicine Program

Merrifield Award from the American Peptide Society:Dr. Charles Deber, Senior Scientist in the Program inMolecularMedicine,ResearchInstitute,Hospital forSickChildren,andProfessorintheDepartmentofBiochemistry,UniversityofToronto,receivedthe2017BruceMerrifieldAwardof theAmericanPeptideSociety. TheAwardwascreatedin1997inhonourofDr.R.BruceMerrifield,whowontheNobelPrize inChemistry in1984.Theaward ispresentedeverytwoyearstoleadersinthefieldwhohavedemonstrated outstanding career accomplishments inpeptideresearch,“recognizingthehighestlevelofscientificcreativity”.Dr.Deber’sresearchfocusesonthehierarchyof forces that characterize the interactions of peptidesand proteins with membranes, and the application oftheseinteractionstodesignnovelpeptideantibioticsandpeptide-basedinhibitorsofbacterialmultidrugresistance.

Canada Research Chair:Dr. Jean-Philippe Julien, ScientistintheMolecularMedicineProgramatSickKids,andAssistantProfessor,Departmentsof Biochemistry and Immunology, University of Toronto,hasreceivedaTier2CanadaResearchChairinStructural

Dr. Vito Mennella

Dr.DanielaRotin

Dr.JohnBrumell

Dr. Michael Moran

Dr. Charles Deber


Immunology. Dr. Julien’sresearch team uses structuraland biophysical techniques tocharacterize how antibodiestarget cell-surface molecules.His research is laying thestructuralfoundationstobetterunderstand immunologicalprocesses associated withcellularandantibodyfunctions.In particular, he uses his

expertisetocharacterizeantibodyresponsesattheatomicleveltoguidetherationalengineeringofvaccinecandidatesagainstmalariaandHIV.Histeamisalsoworkingtowardsthe structure-based design of biologics to deplete cellsthat become dysregulated in autoimmune diseases andcancers.

Christian B. Anfinsen Award from the Protein Society:Dr. Lewis Kay, SeniorScientist in the Programin Molecular Medicine atSickKids, and Professorin the Departmentsof Biochemistry andChemistryattheUniversityof Toronto, has receivedthe 2017 Christian B.Anfinsen Award of theProteinSociety.TheAward

recognizes technological achievement or significantmethodologicaladvancesinthefieldofproteinscience.Dr. Kay’s research focuseson thedevelopmentofNMRtechniques for studying macromolecular structureand dynamics and their application to problems ofbiologicalandclinicalimportance.Hisworkhasledtothedevelopmentof anumberof groundbreaking tools andapproaches thathaverevolutionizedNMRspectroscopyandrendereditoneofthemostpowerfultechniquesinproteinscience.

Scientific Director of the SPARC Facility:Dr. Roman Melnyk, Senior Scientist in the MolecularMedicine Program at SickKids, and Assistant Professorin the Department of Biochemistry at the University ofToronto,hasbeenappointedasScientificCo-Directorofthe SickKids Proteomics, Analytics, Robotics& ChemicalBiologyCentre (termedSPARC),astate-of-the-art facilitythat provides drug discovery services to the research

community on a fee-for-service/cost-recoverybasis, and is designed tobeflexibleandaffordableforacademicresearchers.SPARC Drug Discoveryalso serves as a platformwhere new technologiescan be developed andintroduced. Dr. Melnyk’sresearch employschemical biology and

targeted drug discovery approaches to identify toxin-deliveryplatformstoshuttleotherwisenon-cellpenetranttherapeuticsintocells.

McGill UniversityDepartment of BiochemistryCorrespondent:MartinSchmeing(withMaximeDenis,MarleneGilhoolyandwithphotosfromChristineLaberge)

Asalways,2017wasabusyyearfortheDepartmentofBiochemistry at McGill University. We welcomed Alba Guarné, who joined us fromMcMaster University as aseniorhireattherankoffullProfessor.Maxime Bouchard was promoted to full Professor. Selena Sagan of theDepartmentofMicrobiology&Immunologywasgrantedassociate membership, and Julie St-Pierre, upon hermove to theUniversity ofOttawa, assumed an adjunctappointment.Rod McInnesbecametheActingPresidentof CIHR. Two Department stalwarts, John Silvius andGordon Shore retiredandwereconferred thehonorificdesignation of Professor Emeritus. They have each hadfantasticcareers,havebeeninvaluabletotheDepartment,andtheirdailypresencewillbesorelymissed.

The Department continues to strive to innovate andstrengthen our teaching. One important advance forour undergraduate teaching program in 2017 was thehiring of Dr. Maxime Denis, a new full-time teachingfacultymember.Dr.Denisisdevelopingnewapproachesto teaching undergraduates, such as making BIOC 311(Metabolic Biochemistry) a more interactive coursethrough flipped learning, think-pair-share and in-classdiscussions.Studentsseemtohaverespondedwithgreatenthusiasm.BIOC311 joins a growingbodyof courses,includingBIOC450(ProteinStructureandFunction)andBIOC470(LipidsandLipoproteinsinDisease),infeaturing

Dr.Jean-PhilippeJulien

Dr.LewisKay

Dr. Roman Melnyk


activelearningstrategiestoefficientlyincreasestudents’informationretentionandengagement.Thesestrategieswill be a substantial component of our upcomingundergraduateprogramrevision.Inotherteachingnews,special mentions go toDr. Sidong Huang andMr. Elie Kostantinwhowonthe“Excellence inTeachingAward”and the “Excellence in Teaching Assistant” awards for2017,respectively.

WearinglabcoatsmakeMcGillstudentssmile!

Department members continued to publish excitingresearch results in 2017.Weunofficially tookover theMay2017issueofStructure,includingthecoverillustrationandthreearticlesfromtheBerghuis, GehringandSchmeing labs. Other highlights include the following: Vincent Giguère’s group showed that the mTOR kinase formsa complex with the androgen receptor in the nucleusofprostate cancer cells to control ametabolicprogramfavouring tumour growth (Genes& Dev 31(12)). Imed-Eddine Gallouzi and his colleagues demonstrated thatSTAT3playsakeyroleintheonsetofcancer-inducedmusclewasting in an NF-κB-dependent and IL-6-independentmanner(EMBOMolMed.9(5)).Alba Guarnécontributedto the understanding of how a bacterial assemblyfactor can test out a specific translation mechanismwitha structureof the30S ribosomesubunitbound totheYjeQ (PNAS114 (17)),and tohowCD22 is targetedby therapeutic antibodies (Nat Commun 8(1)). Albert Berghuis’ team elucidated that farnesyl pyrophosphatesynthase, an enzyme of the mevalonate pathway andanticancer target, is regulated by allosteric productinhibition,andprovidedinsightsastohowtoexploitthisnatural feedbackmechanismpharmacologically (NatureCommun8(1)).Martin Schmeingandco-workersgainedstructuralandmechanistic insight intoheterocyclizationdomainsofnon-ribosomalpeptidesynthetases,explaininghow they catalyze both peptide bond formation and

heterocyclizationofthepeptidebackbone(PNAS114(1)).Kalle Gehring’slaboratorypublishedareportdetailinganinterestingparallel-strandedformofpoly(A)RNA(NucleicAcidsResearch45(17)).

Department of Biochemistry faculty members wererecognizedwithavarietyofexternalhonoursandawardsin2017.Dr. Morag ParkwontheRobertL.NoblePrizeoftheCanadianCancerSocietyforherinfluentialbiomedicalcancer research, and leadership in establishingnationalcancerresearchstrategies.Philippe GroswasappointedtotheOrderofCanada,inrecognitionofhispioneeringuseofmoleculargeneticstoidentifyriskfactorsinconditionsincludinginfectiousdiseasesandcancer.Michel Tremblay was awarded the Royal Society of Canada McLaughlinMedal, for his excellent body of work on the role andfunction of tyrosine phosphatases in the developmentof cancer. The Royal Society of Canada also electedJerry PelletierasafellowoftheAcademyofScience,inrecognitionofhisresearchintoproteinsynthesisanditsdysregulationincancer.Martin Schmeingwasgiventhe2017NewInvestigatorAwardfromtheCanadianSocietyforMolecularBiosciencesforresearchintothestructuresandfunctionsofmicrobialmegaenzymes.

The Department had plenty of fun in 2017 as well. OfparticularnotearetheBUGS(BiochemistryUndergraduateSociety)WineandCheese,theBUGSCareerSymposiumand the BGSS (Biochemistry Graduate Student Society)ResearchDay,andtheannualPelletierlab/BiochemistryDepartmentChristmasparty.Anew tradition started in2017withthefirstannualMcGillBiochemistryDodgeballtournament, which was won by the faculty team, TheProfessorsofDoom.Themanystudentteamswillbeoutforrevengein2018.Moreglimpsesintodepartmentallifecan be found at https://www.facebook.com/mcgillbioc/andhttps://www.mcgill.ca/biochemistry/about-us/events/community

Amap,aplateandanordinaryMcGillscientist


JulianaMuñoz-Escobar,bestposterwinner,BGSSResearchDay!

Ready,set,dodge!

McMaster UniversityDepartment of Biochemistry and Biomedical SciencesCorrespondent:JohnWhitney

2017marked another exciting and productive year for ourdepartment.Our chair,Karen Mossman,was promoted toAssociate Vice President Research. For the past 4.5 years,Dr.Mossman has overseenmany notable advances in ourdepartment including the formation of the BiomedicalDiscovery and Commercialization program and numerousnew faculty hires. Dr. Mossman was succeeded by Brian Coombes,whobeganhis5-yeartermaschairatthebeginningof 2018. Dr. Coombes, a Tier 2 Canada Research Chair inInfectious Disease Pathogenesis, leads a highly successfulresearch program studying the evolution of virulence inenteropathogenicbacteria.Dr.Coombeshasambitiousgoals

forourdepartmentandwelookforwardtoseeinghimenacthisvisioninthecomingyears.In2017,wealsocelebratedthe50th anniversary of Biochemistry and Biomedical Sciences(BBS),whichculminatedinaday-longeventandreceptionthat included many currentand formermembersofourdepartment. Among themany highlights of the daywas a stimulating talk onthe commercialization ofscience by keynote speakerand McMaster alumnusBrianBloom,co-founderandCEOoftheleadingCanadianhealthcare investmentbanking firm Bloom Burton&Co.

DepartmentofBiochemistryandBiomedicalSciences50thAnniversary:pastandpresentdepartmentchairs(lefttoright;EricBrown,GerhardGerber,HaraGhosh,JohnCapone,KarenMossman,GerryWright,DennisMcCalla,KarlFreemanandBrianCoombes)werepresenttocelebratepastaccomplishmentsandfutureendeavours

2017 saw the addition of three new faculty membersto our department: John Whitney, Sara Andres andJakob Magolan.JohnWhitneyobtainedhisPh.D.intheDepartmentofBiochemistryattheUniversityofTorontoin2013beforemovingtoDepartmentofMicrobiologyattheUniversityofWashingtonforpost-doctoraltraining.His lab employs genetic, biochemical and structuralapproaches to understand toxin secretion by bacteria.SaraAndrescompletedherPh.D.intheBBSDepartmentat McMaster before doing post-doctoral training inthe Structural Biology Division at NIEHS in Durham,North Carolina. Dr. Andres’ lab studies the molecularmechanisms underlying DNA repair. Jakob Magolan

Dr.BrianCoombes,newlyappointedchairoftheBiochemistry and Biomedical Science Department


did his Ph.D. at Queen’s University and post-doctoraltraining at the Griffith University Institute for DrugDiscoveryinAustralia.HewasthenhiredasanAssistantProfessor at the University of Idaho, where he ran asuccessful researchprogram for7 yearsbeforemovingtoMcMaster.Dr.Magolanisamedicinalchemistwhoseresearch interests lie in the hit-to-lead optimization ofcompoundsinanumberoftherapeuticareas,aswellasthedevelopmentofusefulnewsyntheticmethodologies.The senior faculty in our department have done anexcellentjobhelpingthenewrecruitsgettheirresearchprogramsupandrunninginanexpedientmanner.

NewBBSfacultymembers:JohnWhitney(left),SaraAndres(middle)andJakobMagolan(right)joinedourdepartmentin2017

Thispastyearwasalsohighlightedbymanyoutstandingdiscoveriesbymembersofourdepartment.Themajorityofourfacultymembersareassociatedwithoneofthreemajor research institutes at McMaster. Members ofthe Michael DeGroote Institute for Infectious DiseaseResearch(IIDR)mademanyseminalcontributions inthefields of bacteriology and antimicrobial resistance. Eric Brown found that the antibiotic colistin potentiates theactivity of other antibiotics (Nature Comm, 9:458). HislabalsopublishedanelegantstudyonthemechanismofcellwallbiosynthesisinGram-positivebacteria(Cell Chem Biol, 24:1537). Lori Burrows discovered that bacteriadisguise their virulence factors to avoid predation byinfectiousbacteriophage(Nature Micriobiol,3:47).Gerry Wright’slabuncoveredauniquemechanismofenzymaticinactivation of the antibiotic rifamycin by rifamycinmonooxygenases (Cell Chem Biol, in press). Faculty inourStemCellandCancerResearchInstitute(SCC-RI)alsomademany significant contributions to theirfield.Mick Bhatia discovered a previously underappreciated linkbetweenbonebarrowadipogenesisandmyelo-erythroidmaturation (Nature Cell Biol, 19:1336). His group alsoidentifiedasmallmoleculethatmodulatesWnt/β-cateninsignallingwithinhumancancerstemcells(Cell Chem Biol, 24:833).Bradley Doble and his teampublished a study

showing that a single member of a redundant groupof transcription factors is sufficient for differentiationof embryonic stem cells (Cell Reports, 20:2424). In ourFarncombe Family Digestive Health Research Institute,Jonathan Schertzer discovered that constituents of thebacterialcellwallcanfunctionaspostbioticsbysensitizingcellstoinsulin(Cell Metabolism,25:1063).

BBS faculty continued to achieve high success rates inresearchfundingcompetitionsandfacultyawards.IntheFall 2017 CIHR Project Grant competition, funding wasawardedto John Whitney, Lori Burrows, Brian Coombes, Kristen Hope, Lesley MacNeil, Andrew McArthur andDino Trigatti. Jonathan SchertzerwastherecipientofaprestigiousCIHRFoundationGrant.2017NSERCDiscoveryGrantRecipientsincludedJohn Whitneyand Yu Lu,whileGerry WrightwasawardedanNSERCInfrastructureAward. Yingfu Lihadaverysuccessfulyear,obtainingfundingfromboththeCIHRAntimicrobialResistanceStrategicInitiativeandtheNSERCStrategicPartnershipfundingcompetition.Notablefacultyawardsincludeda2017YWCAWomanofDistinctionAward toDeborah Sloboda andaMcMasterUniversityFacultyAssociationAwardtoLori Burrows for Outstanding Service. Lori Burrows was also elected asa Fellow of the American Academy ofMicrobiology, anexclusivegroupcomprisingtheworld’smostaccomplishedmicrobiologists.

41stAnnualYWCAWomenofDistinctionAwardsCeremony:DeborahSloboda(left)celebratesherawardwithhernominator,BBSfacultymemberLesleyMacNeil(right)

LoriBurrowsMUFAaward.jpgcaption:McMasterUniversityFacultyAssociationAwardsCeremony:LoriBurrows(left)receivesanOutstandingServiceAwardfromhernominator,BBSfacultymemberMichelleMacDonald(right)


This past fall we welcomed our incoming cohort ofgraduate students,which consistedof26M.Sc., 8Ph.D.and 1M.D./Ph.D. candidates. Graduate students in ourdepartmentcontinuetoobtainscholarshipsatahighrate,with 23 major external scholarships being awarded in2017.AmongtheseawardwinnerswasPh.D.studentBeth CulpfromGerryWright’slab,whowasawardedahighlycompetitiveVanierCanadaGraduateScholarship.TheKarlFreemanawards,givenouttostudentswhoweredeemedto have given the best presentations in our graduatestudentseminarseries,wereawardedtoAndrew Tupper (1stplace,Higgslab)andRobert Gale(2ndplace,BrownLab)inthePh.D.categoryandMadeline Tong (1stplace,BrownLab)andLinda Liu (2ndplace,GuarnéLab).AtourInstitute of Infectious Disease Research Annual TraineeDay, Stephanie Jones (Ph.D., Elliot Lab), Allison Guitor (M.Sc.,WrightLab),andDaniel Celeste (Undergraduate,MillerLab)wereawardedMichaelKaminHartMemorialScholarships. These awards are made possible by thegeneroussupportoftheHartfamily.

BiochemistrynewstudentwelcomeBBQ2017:Studentsoftheincominggraduateclassof2017werewelcomedtoourdepartmentbyfacultyandstaff

Ph.D. student Beth Culp from Gerry Wright’s lab was awardedaprestigiousVanierScholarshiptosupportherresearchonantimicrobialresistance

In keeping with the “work hard, play hard” cultureof our department, we had a record turnout for theBiochemistryOlympics,whichareheldduringtheannualBBSdepartmentalpicnic.Inthislab-themedpentathlon,teams compete at events that reward both textbookknowledgeandmanualdexterity–twoessentialskillsofasuccessfulscientist.Inthefaceofstiffcompetition,thegoldmedalwenttotheBrownLab,followedbysilvertotheSlobodaLabandbronzetothefacultyteam.

AnnualBBSpicnic:biochemistrystudentsandBBSfacultymemberMatthewMiller(secondfromright)participateinourannualBiochemistryOlympicsheldduringthedepartmentalsummer picnic

Princess Margaret Cancer Centre, TorontoCorrespondent:GilPrivé

AfteralongandsuccessfulrunastheExecutiveVicePresidentofScienceandResearchattheUniversityHealthNetwork,Dr. Chris Paige stepped down from the position in ordertorefocushisenergyonhislabandresearch.Followinganinternationalsearch,hisreplacementwasfoundwithinourranks. Dr. Brad Wouters, who served as Interim ResearchDirectorofthePMCancerCentresince2014,acceptedtheposition of UHN EVP for Science in October 2016. In thisrole,heisresponsibleforthefiveconstituentUHNhospitalresearch institutes, including the Princess Margaret. Dr. Rama Khokha did anadmirable jobas InterimDirectorofthePMresearchinstitutefromOct2016toNov2017,andhandedoffthereinstothecurrentInterimResearchDirector,Dr. Mitsu Ikura,withDr. Aaron ShimmeractingastheInterimAssociateResearchDirector.


On November 24, 2017, The Honorable Kirsty Duncan,Minister for Science, visited the PM Cancer Centre andtouredthefacilitiesandlabsatthePrincessMargaretCancerResearch Tower (PMCRT). She was highly engaged in herdiscussionswithPMscientists,afactthatbodeswellfortheengagementofthefederalgovernmentonscienceissues.

Research highlights:InapaperinNatureGenetics,PMScientistDr. Hansen He hasshownthatPCAT1,a longnon-codingRNA,promotesprostate cancer tumour growth. Previously considered“junk”DNA,regionscodingforlncRNAshavebeenassociatedwithcancerrisk,butthispaperprovidesafirstmechanisticviewofhowthesenucleicacidscandrivebiology.

Whyaremostenzymesoligomeric?PMSeniorScientistDr. Emil Pai and University of Toronto Professor Scott Prosser have shown how the two chains of a proteinengage in “cross-talk” in regulating the activity of ahomodimeric enzyme. By analyzing a large numberof crystal and NMR structures of fluoroacetatedehalogenase,theteamdiscoveredanasymmetryintheenzyme inwhich disorder in one active site drives theactivityoftheother.Thefindings,publishedinScience,mayrepresentafundamentalmechanismforincreasingtheefficiencyofcatalysisinothermulti-chainenzymes.

Dr. Mitsu Ikura has reportedthattheoncogenicpropertiesoftheMLL-AF6fusionproteinare the result of an induceddimerization in the abnormalgene product (NatureCommunications). The fusionexposes a hydrophobic patchin MLL-AF6, which causesdimerization and promotesassociationwithkeymediators

ofgeneexpression.Remarkably, inhibitingdimerizationcompletelyblocksMLL-AF6leukemogenesisinmice.

Awards and honours:Congratulations to the following PM Cancer Centrescientistswhowereawardedor renewed theirCanadaResearch Chairs: Tier 1:Dr. Brad Wouters (new 2017),Dr. John Dick (renewed2016),Dr. Mitsu Ikura(renewed2018); Tier 2: Dr. Daniel De Carvalho (new 2016),Dr. Thomas Kislinger(renewed2016).

Dr. Gordon Keller,whohaspioneeredmethodstoguidepluripotent stemcells intovarious cell types,hasbeenelectedasaFellowof theRoyalSocietyofCanada.Dr. Hansen He has received one of three Terry Fox NewInvestigatorAwardstosupporthisworkoncircularRNAintumourhypoxia.Drs. Daniel De CarvalhoandMathieu Lupien are the co-recipients of the Canadian CancerSociety Bernard and Francine Dorval Prize for younginvestigators whose contributions to basic biomedicalresearchhavethepotentialtoimprovecancertreatment.

Dr. Chris Paige has been recognized for his work inchampioning health research with the 2017 ResearchCanada Leadership in Advocacy Award. He hasalso received the UHN Inventor of the Year for hiswork in immune-oncology. The technology is beingcommercializedwithAvroBioInc.

Dr. John Dick continues to receive recognition on hiswork on the identification and characterization ofleukemia stem cells, and has recently received twoprestigiousprizes:theCIHRGoldLeafPrizeforDiscoveryand the 2017 Keio Medical Science Prize. Dr. Dick’sCIHR awardwill be presented to him by theGovernorGeneralduringaceremonyinOttawaonMay16.Theseawards recognize his outstanding contributions to ourunderstandingof cancerbiology, andhis global impact

Dr.HansenHe Dr.EmilPai

Dr.Mitsu Ikura

Dr. Chris Paige Dr.JohnDick


of on the scientific community. As always, John wasgenerous in acknowledging the essential contributionsofhismanystudents,post-docsandcolleagues.

Ryerson UniversityDepartment of Chemistry and BiologyCorrespondent: Roberto Botelho

TheDepartmentofChemistryandBiologyencompassesmulti-disciplinary interests in research and education.Our Chemistry research programs are generallyfocussed onmacromolecular, synthetic andmedicinalchemistry. The research interests in Biology enjoystrengthsrangingfrombiochemistry,molecularandcellbiology to genetics, microbiology and environmentalbiology. Thebreadthandvarietyof research interestscreatesanexceptionalenvironmentthatpermitscross-pollination of ideas and an open-concept milieu forlearningandteaching.Lastyear,wehadseveralnotableeventsworthsharingwiththeCSMBcommunity.

New faculty member:In2017,ourdepartmentcontinueditsgrowthtrajectorybyrecruitingDr. Gagan Gupta.Dr.Guptabringstothe

department his expertisein functional genomicsand centrosomal cellbiology, specializing inboth protein-interactionmethods and highcontent imaging. Dr.Gupta’s research willfocus on using proteininteraction networks tounderstand ciliopathiesandmembranetraffickingdiseases.

Awards, recognition and publications:Our researchers have published inMol. Biol. Cell, J.Cell Biol., J. Immunol, PNAS, J. Cell Sci., and ClinicalProteomics,amongothers,withnoveldiscoveriesrelatedtophagocytosis,endocytosis, receptor tyrosinekinasesignalling, host-pathogen interactions, glycobiology,proteomicbiomarkers,andphosphoinositidesignaling.Ashighlights,wepointtoNaufer,Hipolitoetal.,J.Cell

Biol. which identified the luminal pH of phagosomesand endosomes as a regulator of phosphoinositidesynthesis,andDelosSantosetal.,Mol.Biol.Cell,whichexamined the role of phospholipase C and calcium inEGFRsignallingandendocytosis.

Special events:Ryerson University, its Department of Chemistry andBiology,andtheFacultyofScience,wasamajorsponsorofthe2017CanadianSocietyforMolecularBiosciencesMeeting that took place in Ottawa from May 16-20,entitled “CelebratingCanadianMolecularBiosciences:fromOrganellestoSystemsBiology”.Thiswasarguablythemost successful CSMBmeeting todate, attracting420registrantsacrossSystemsBiologyandCellBiologycommunities in Canada. Dr. Costin Antonescu andRoberto Botelho were members of the organizingcommittee.

Our department continues to be a key participant inRyerson’s“ScienceRendezvous”thatraninMay2017.Thiswasthe10thScienceRendezvoushostedatYonge-Dundas Square, arguably the busiest intersection inToronto. Open to the public, it easily attracted over10,000 visitors by showcasing research, hands-onactivities,displaysand stage shows thatdelighted theaudienceanddemonstratedhowscienceplaysapartinoureverydaylives.

We also held our first Departmental Retreat on thebeautiful shores of Lake Simcoe, where we had theopportunity to plan how to best integrate chemistryinto biological research and teaching. This is just oneof several efforts that we pursued to foster inter-disciplinaryresearchandunderstanding.

Lastly,wehostedour6thAnnualResearchSymposiumwithmorethan80posterpresentationsandmorethan10 talks. These showcased our exciting and emergingresearch activities across various disciplines, andhighlighted both undergraduate and graduate-basedresearch activities. Dr. Laura Hug from University ofWaterloowasthekeynotespeaker.

Dr.GaganGupta


Simon Fraser UniversityDepartment of Molecular Biology and BiochemistryCorrespondent:ChristopherBeh

Togetherwithnewsonfacultyandstudentachievements,this report for the MBB Department at SFU includesnotableprogramchangesduring2017thatenhancedourresearchandteaching.WecontinuetoencourageallourMBBDepartmentalumnitocontactusatmbbalumni@sfu.ca so we can hear about your career paths andsuccessessinceyourdaysatSFU.

Department highlights:We congratulate one of our newest faculty members,Dr. Tim Audas, on his successful award of a Canada Research Chair (CRC) Tier 2. Dr. Audas investigatesnon-coding RNAs and their involvement in a stress-responsepathwaythatgeneratesreversibleamyloid-likestructures.WealsoapplaudDr. Ryan Morinonbecominga MichaelSmithFoundationforHealthResearch(MSFHR)scholar.InadditiontothedistinctionofbeingaCIHRNewInvestigator,Dr.Morinhasreceivedgreatrecognitionforhisuseofhigh-throughputsequencingandbioinformaticsto identify driver mutations that contribute to cancermalignancy. We commend the research achievementsof all our faculty who have done exceptionally well innationalandinternationalawardcompetitions.

Meetings and new research groups:Thispastyearsawthefirstannual“CentreforCellBiology,Development and Disease (C2D2)” symposium, held attheSFUHarbourCentrecampusindowntownVancouver,whichwasanoutstandingsuccesswithover100attendees.C2D2wasfoundedin2014asanorganizationtofacilitatecollaboration between SFU researchers working on celland developmental mechanisms that affect disease(http://www.sfu.ca/c2d2.html).AsoneofthecontributingDepartments, MBB is working with other research andacademicunitsatSFUtopromoteopportunitiesthroughnewinteractionamongstfacultyandtrainees.

Although genomics and bioinformatics have alwaysrepresented one of the bedrock disciplines of ourDepartment, an “Omics Group” was inaugurated thispastyeartobringthelargerSFUcommunitytogetherforintegratedstudiesin“omics”.Thisstudent-ledefforthassuccessfully connected many students, post-docs, andfacultyinworkshopsandmeetings.

Student awards and other news:Among the many awards received by our graduatestudents and post-docs, three awards are particularlynotable. Ms. Kristen Gray received a CIHR FrederickBantingandCharlesBestCanadaGraduateScholarship andMr. Justin JiareceivedanNSERCCREATEscholarship.Both graduate students represent themany successfulbioinformatics trainees in Dr. Fiona Brinkman’s lab. In addition, Mr. Kurt Yakimovich was awardedan SFU Graduate Dean’s Doctoral Scholarship. Our undergraduateshavealsonettedprestigious awards.ASchulich scholarshipwasawardedtoMs. Jasmine Rai in recognition of her impressive academic record in highschool.AsanundergraduatestudentatSFU,Ms.Rai iscontinuingSTEM-relatedstudiesinourMBBjointmajorprogram with computer science. Mr. Andy Zeng, also a former Schulich scholarship awardee, graduated thisyear after earning the Gordon Shrum UndergraduateMedalforhismanyacademicachievements.HehassincemovedontotheUniversityofTorontofortrainingintheirMD/PhDprogram.

Sunnybrook Research InstituteBiological Sciences PlatformCorrespondent:DavidAndrews

Our scientists in the Biological Sciences Platform atSunnybrook Research Institute (SRI) are striving tounderstand how biological systems function in healthyanddiseasestates.Amongourresearchareasaretumourbiology, protein-protein interactions, immune systemdevelopment,andneurodegenerationand regeneration.Areas of disease interest include cancer, cardiovasculardisease, brain disorders like stroke and dementia, andtraumaticinjury,acuteandacquired.

Research grants and awards:Dr. Juan Carlos Zúñiga-Pflücker, a senior scientist andChairoftheDepartmentofImmunologyattheUniversityof Toronto, was awarded a Foundation Grant from theCanadianInstitutesofHealthResearch(CIHR)worth$2.8million.HisresearchcentresontheroleofNotchsignallinginT cell developmentand the functionof those cells inimmuneregulation.


Two SRI scientists were successful in CIHR’s Fall 2017ProjectGrantcompetition.Dr. JoAnne McLaurin,aseniorscientist,willreceive$933,300overfiveyearstogeneratenew neurons from glial cells in thememory centre of apreclinical model of Alzheimer’s disease. As part of thisprojectsheiscollaboratingwithDrs.CarolSchuurmansandBojana Stefanovic, senior scientists in Biological Sciencesand Physical Sciences, respectively, to study a treatmentstrategy forAlzheimer’sdisease that aims tobalance theneuronalnetworkbyconvertingastrocytes into inhibitoryneurons.Dr. Burton Yang,aseniorscientist,wasawarded$990,675overfiveyears to study the roleof thecircularRNAcirc-Itga9incardiacremodelling.

Dr. Carol Schuurmans, a senior scientist and theDixon Family Chair inOphthalmology, receiveda Discovery Grant fromthe Natural Sciences andEngineering ResearchCouncil of Canada. Thegrant, worth $200,000, willfund her research on themolecular mechanismscontrolling Müller glial cellactivationintheretina.

ThreecancerresearchersatSRIreceivedgrantfundingtoadvance theirwork.Dr. Robert Kerbel, a senior scientist,was awarded a grant worth £189,132 ($239,635 CAD)from Worldwide Cancer Research to develop a newanti-angiogenic therapy that targets vessel co-option inmetastatic cancers.Dr. Arun Seth, also a senior scientist,received a one-year grant from the Ontario MolecularPathology Research Network. The grant, worth $34,800,will support his work looking for markers predictive ofprogestin therapy response in conditions that affectthe endometrium. Dr. Stanley Liu was awarded a 2017MovemberDiscoveryGrant fromProstateCancerCanadatolookforgeneticandproteinbiomarkersthatcanidentifypatients whose prostate cancer are more likely to recurafterradiationtreatment.

Dr. Laurence Klotz,anaffiliatescientist,waspresentedwiththeDean’sLifetimeAchievementAwardfromtheUniversityofTorontoFacultyofMedicine.Theawardrecognizesalumniwho have made outstanding contributions to research,teaching,clinicalcare,administrationorpublicservice.

Research highlights:Dr. James Carlyle’s group has identified the firstphysiological ligand for the prototypical NK1.1 receptor,a member of the NKR-P1 family of natural killer (NK)cell receptors. The researchers showed that themurinecytomegalovirus-encoded protein m12 binds directly totheinhibitoryNKR-P1BreceptortoinhibitNKcellfunction.Thestudy,whichwaspublishedinCell,foundthattheviraldecoyproteinalsointeractedweaklywiththestimulatoryreceptorsNKR-P1AandNKR-P1C inwhat appears to beanexampleofhostadaptationtoaviralimmuneevasionstrategy.

AstudyfromthelabsofDrs. Michele Anderson andJuan Carlos Zúñiga-Pflücker hasdemonstrateda requirementforthetranscriptionfactorHEBinmesodermdevelopmentandpre-hematopoieticevents.TheteamusedCRISPR-Cas9toknockoutHEB inhumanembryonic stemcellsbeforeinducingthemtodifferentiateintoTcells.TheyfoundthatlossofHEBledtodefectsinmesodermdevelopmentandhemogenic endothelium formation as well as a failureof T cell development. Their results, published in Stem Cell Reports, indicate that HEB is a crucial regulator inmesodermandhematopoieticspecificationduringhumanembryogenesis.

In a study published inCell Chemical Biology, Dr. David Andrews’ group identified small molecule inhibitors ofBax/Bakoligomerization.BaxandBakaremembersoftheBcl-2familyofproteinsthatregulateapoptosis.Andrews,a senior scientist anddirectorof theBiological Sciencesplatform, and his team of international collaboratorsdiscoveredandcharacterizedthreesmallmoleculesthatblockBax/Bakoligomerizationandpreventmitochondrialoutermembranepermeabilization,therebyallowingcellstoevadeapoptoticstimuli.

Dr. Carol Schuurmans, seniorscientistatSRI

Dr.OscarAguilar,formerPhDstudent in the Carlyle lab

Dr.MicheleAnderson,seniorscientistatSRI


Université de SherbrookeDépartement de biochimieCorrespondent:MichelleScott

2017 saw a wind of change within the Biochemistrydepartment, the Faculty of Medicine and HealthSciences, and the Université de Sherbrooke. ProfessorJean-PierrePerreault,previouslyVice-DeanofResearchandofGraduateStudies intheFaculty,andmemberofthe Biochemistry department, became Vice-Rector of

Research and of GraduateStudies for the university.Department chair MartinBisaillonbecameSecretaryofthe Faculty andVice-dean ofstudent life.Finally,ProfessorXavier Roucou, who headsa dynamic group studyingthe alternative proteome,becameheadofdepartment.

Our 23rd annual graduate symposium held in March2017, co-organized by our two graduate studentrepresentatives, Ariane Brault and Andréa Allaire, aswell as by Prof. Michelle Scott, was a success. Prof.Gary Kobinger from the Université Laval, our keynotespeaker,discussedthechallengesofquicklydevelopingvaccinesandtherapiestoemerging infectiousdiseases,and his experience with the Ebola outbreaks, whileJean-François Denis, invited Ph.D. student from theUniversité de Montréal, presented on the differentialactivationofSmadsintheprocessofregeneration.10UdeSherbrookegraduatestudentsfromtheBiochemistrydepartmentpresentedtheirresearch.Thefinalistswerethefollowing:HélèneMouilleronfromtheRoucougroup

wonfirstprize,FannyThuriotfromtheLévesquegroupwonsecondprize,whileLouis-PhilippeMorencyfromtheNajmanovich groupwon third prize. Simon Boudreaultfrom the Bisaillon labwon the Pierre-Chailler prize forbeststudentoftheyear.

Prizes and distinctions:Professor ÉricMassé,whose group characterizes smallregulatory RNAs in bacteria, won the Research andCreativityAwardoftheUniversity,whilehispost-doctoralfellow,DavidLalaouna,obtainedtheMarieSkłodowska-Curie Fellowship. Ph.D. student Jean-François LemayfromProfessorFrançoisBachand’sgroupwontheprizeforthebestthesisbothattheUniversitédeSherbrookelevel and from the Association des doyens des étudessupérieuresduQuébec.

University of AlbertaDepartment of BiochemistryCorrespondent:JoeCasey

Events:In November 2017, the Department held a retreat,coordinated by our stellar Teaching Professors, Drs. Rachel Milner, Adrienne Wright and Jo Parrish, whichfocusedprimarilyonteachinginitiativesanddelivery.Theresult was a productive and well-engaged event whichledtomanysuggestionsonhowtoimprovethelearningexperienceforourundergraduatesandgraduatestudents.

On June 15, 2017 we celebrated the 50-year researchcareer of Dr. Michael James, Distinguished UniversityProfessor(Emeritus),whostartedworkattheUniversityofAlbertain1968.Over100departmentmembersattendedthe celebration. Former lab members from around theworld – U.S.A., Switzerland, Australia, Ireland, and theU.K. - came for a symposium, with talks from formertrainees:Dr. Randy Read (UniversityofCambridge,UK), Dr. Natalie Strynadka (UBC), andDr. Amir Khan (TrinityCollege,Ireland).TheeveningendedwithadinnerattheUniversity of Alberta Faculty clubwhere all participantssharedfunstories.

Faculty news:Dr. Dennis Vance, who is now working 1/3 time as aProfessorEmeritus,wasinvitedbytheJournalofBiologicalChemistrytowriteahistoricalaccountofhiscareerinlipidbiochemistry. Check out “Frommasochistic enzymology

Newdepartmentchair, XavierRoucou

Graduate Symposium 2017. Top row from left: Martin Bisaillon,SimonLabbé,GaryKobinger,Jean-FrançoisDenis.Bottomrowfromleft:Louis-PhilippeMorency,ArianeBrault,FannyThuriot,HélèneMouilleron,AndréaAllaire,MichelleScott


to mechanistic physiology and disease” at http://www.jbc.org/content/292/42/17169.full?sid=17085a46-4437-4418-836e-a078106d725d

To celebrate his move to emeritus status, Dr. Dennis VanceorganizedameetingattheBanffCentreonAugust27-31,with80scientists from8countries,allofwhomhadbeeneithera traineeorcollaboratorofDennis,orDr. Jean Vance.

AttendeesatDennisandJeanVance’smeetinginBanff

Retired former Chair, Dr. Vern Paetkau, is living inVictoria,BC,wherehereportsthatlifeisgreat.

FormerChair, Dr. Vern Paetkau,enjoying2017post-retirementactivitiesnearVictoria,BC

OneofourstudentsMelissa McLellanfinishedhermaster’sprograminbiochemistryattheUniversityofAlbertaandearned a competitive Ph.D. scholarship at The Francis CrickInstitute inLondon,aprestigiousandglobally-renownedhub for health science research, under the direction ofNobelPrizelaureate,SirPaulNurse.Melissawasoneof40selectedstudentsoutofmorethan1,000applicants.ShestartedherprograminSeptember,withresearchfocusontheroleofproteinphosphatasesintissuearchitectureandcellgrowthcontrol.

Newassistantprofessors, Drs. Sue Ann MokandOlivier Julien, successfully completed their move from theUniversityofCaliforniaSanFranciscotonewlyrenovatedlaboratoriesinBiochemistryinAugust2017.

SueAnnMokandOlivierJulien

Graduations:Anamika (Ph.D.; Spyracopoulos), Aruna Augustine(M.Sc.; Fliegel), Mohamed Eldeeb (Ph.D.; Fahlman),Rebecca Gibeault (Ph.D.; Schang), Melissa McLellan(M.Sc.;Holmes),RobynMillott(M.Sc.;Holmes/Glover),Rory Shott (M.D./Ph.D.; Schang), Sietske Speerstra(M.Sc.; Schang),Carmen(KaYee)Wong(M.Sc.;Fliegel).

Special lectures:The Department of Biochemistry has two namedlectureships. This year there were two John S. ColterLectures:inJune,asaleadoffforthecareercelebrationconferenceforDr. Michael James, Dr. Stephen Withers FRS, Department of Biochemistry at UBC, presented“Discovery,designanddevelopmentofhumanamylaseinhibitors: from nM to pM”, and in August, as a leadoffforthecareercelebrationconferenceforDr. Dennis Vance, Dr. Stephen Young (UCLA)presented“Triglyceridemetabolismalongthecapillarywall“.

JoParrish,RandyRead,MichaelJames,NatalieStrynadka,AsmirKhanandJoanneLemieuxattheJune2017CareerCelebrationeventforMichaelJames


InvitedguestsforMichaelJames’CareerCelebration

The Annual William A. Bridger lecture was presented inMarch by Dr. Brian Mark, Department of Microbiology,University of Manitoba, on “Corrupting the ubiquitinsystem:aviralstrategytoevadehostimmunity.”

Obituary:Dr. Neil Madsen (1928-2017) was a longtime facultymemberintheDepartmentofBiochemistrywhoretiredin1993.HiscareeriswonderfullysummarizedinanobituarypublishedinTheTimesColonist:

“Neildistinguishedhimself in thefieldofbiochemistryattheUniversityofAlberta.Hewasagreatscholarofworld-class stature. His legacy in science is well entrenched inthe historical record. After receiving the GoldMedal foracademic excellence in his class in Agriculture at the Uof A, he beganMasters studies in 1950. He received hisPh.D. at Washington University in 1955, under NobelPrizeco-winnersCarlandGertyCori.Hesubsequentlydidpost-doctoral training in the laboratory of anotherNobelPrize winner, Hans Krebs, at Oxford. His life work wasglycogen phosphorylase. He and X-ray crystallographerRobert Fletterick made the discovery of the detailed,complicated structure of that enzyme, crucial to human

andanimalmetabolism.Lateron,Neildidrelatedworkonglycogen-debranchingenzyme.HecollaboratedwithotherresearchersaroundtheworldandhadmanyCanadianandforeign doctoral and graduate student, and post-doctoralfellowsbenefitfromguidanceinhisownlabinEdmonton.HewasalsopresidentoftheCanadianSocietyofBiologicalSciences, a Fellowof theRoyal Society of Canada, and arecipient of the Order of Canada and the Queen’s SilverJubileeMedal.”

University of AlbertaDepartment of PhysiologyCorrespondent:EmmanuelleCordat

TheDepartmentofPhysiologyattheUniversityofAlbertahas been thriving over the past year! Not only have wepersisted in being highly successful in securing externalresearch fundsandpublishinghigh-impact,peer-reviewedscientific publications, but we have also continued hiringnewAssistantProfessorstotakeoverthepositionsofourretiredcolleagues.

Achievements:In 2017, our department and importantly, our newestrecruits,havebeenverysuccessfulatsecuringresearchfundsinahighlycompetitive fundingperiod.OurnewAssistantProfessors,Drs. Silvia Pagliardini, Robin ClugstonandJessica Yue arenowallcurrentlyfundedby5-yearCIHRoperatinggrantsthatwereeitherawardedin2017ortheyearbefore.OurdepartmenthasalsoincreaseditsfundingfromNSERC,sinceDrs. Elaine Leslie, Robin Clugston andEmmanuelle Cordat secured three additional 5-year Discovery grantsin2017.Asproofof thedynamicand innovativeresearchoccurringinourdepartment,33peer-reviewed,high-impactpublications have been published over the past year bythe 17 principal investigators appointed primarily to ourdepartment.Finally,teachinginourdepartmentreachedanewlevelin2017!InSeptember,ourdepartmentlaunchedthe first province-wide on-line Human Physiology course,whichhasreceivedalotofenthusiasmamongstudentssofar,with69studentscurrentlyregistered,includingparticipantsfromCalgary,Grande-PrairieandevenBritishColumbia!

Retirements and new recruits:In2017,wehavecelebratedtheretirementofourcolleaguesDrs. Anthony Ho and Steve Harvey. Dr. Ho closed hislaboratoryandretiredinJune2017,andDr.Harveyiscurrentlyenrolled in the Transitional Retirement Implementation

2017ColterLecturer,Dr.SteveWithersFRS


ProgramuntilJune2018.WethankDrs.HoandHarveyfortheirmanyyearsofhardworkinourDepartmentandwishthemallthebestintheirnewendeavours!Ourlatestrecruit,Dr. Jesse Jackson willstartinourdepartmentinMarch2018.

Overall, in 2017, the Department of Physiology hascontinued its tradition of excellence by successfullyrecruiting outstanding new Assistant Professors,maintaining the diverse yet complementary breadth ofresearchandteaching,andimplementinganewPhysiologyon-line course that appears to become increasinglypopularamongundergraduatestudentsandthatwehopetoexpandsoonbeyondthelimitsofourprovince.

University of CalgaryDepartment of Biochemistry & Molecular Biology, Cumming School of MedicineCorrespondent:JonathanLytton

Twenty-seventeenhasbeenagoodyearintheDepartmentof Biochemistry&Molecular Biology at theUniversity ofCalgary,withseveralsignificanthighlights.

We were very excited to welcome Dr. Maja Tarailo-Graovac tothedepartment inAugust.MajaobtainedherPh.D. from the University of British Columbia inmedicalgeneticsandthendidpost-doctoralworkatSimonFraserUniversity before taking a genome analysis lead position

inthe“Omics2TreatID”and“TIDE-BC” projects. Majanow joins our group ofdevelopmental moleculargeneticistswith an excitingresearch program focussedon understanding thegenetic contributionsto phenotype variabilityin rare genetic disease,which bridges the worldsof human disease geneticsandmodelorganisms.

WealsowelcomedMarkus Eszlingerasanadjunctmemberofthedepartment.

This year marked the retirement of Don Fujita. Don was one of the longest serving members of this department,havingjoinedusfromtheUniversityofWesternOntarioin

1986.Donhadadistinguishedresearchcareerstudyingthemolecularmechanismsofthec-srconcogeneanddevelopingapproachestotargetthisgeneforcancertreatment.Don’smanycontributionstothedepartmentwillbemissed,butwewishhimwellinthenextstageofhislife.

Fundingsuccess,thoughobviouslynotsharedbyall,wasapositivethemefortheyear.OurmembershadparticularlystrongshowingsinbothNSERCandCIHRcompetitions.Inaddition,thedevelopmentalmoleculargeneticists inthedepartmentwhoarepartofthe“GenesDevelopmentandHealth” theme group of the Alberta Children’s HospitalResearch Institute were successful in obtaining a largeCFI grant to support a precisionmedicine for childhooddiseaseresearchprogram.

Mayi Arcellana-Panlilio continues to excel in her roleas Senior Instructor in the Bachelor of Health Sciencesprogram.ThisyearMayireceivedtheUniversityofCalgary’s2017KillamAwardinUndergraduateMentorship,andtheiGEMteamsheledwonagoldmedalattheBostonGiantJamboreefortheir“Astroplastic”project.

Each year our department holds a scientific “advance”meeting in Banff, where we recognize research andeducationalachievementsofbothourfacultyandgraduatestudents. This year Sarah Childs received the “SchultzAwardforGeneralExcellence”,Jennifer Cobbthe“AssociateProfessor Award”, Tara Beattie the “Hans van de SandeLeadership & Service Award” and Randy Johnston the“EducationAward”.Inaddition,graduatestudentsMegan Wong, Heather PaulandKatie Greenewererecognizedfortheiroutstandingcontributions.

BMBstudentspartylikeit’sthe1980satourannualBanff“advance”meeting

NewBMBAssistantProfessor,Dr.MajaTarailo-Graovac


BMBattheUniversityofCalgarycontinuestogrowandflourish, andwe are recruiting both new students andfaculty.Pleasevisitourwebsiteathttp://www.ucalgary.ca/bmb/formoreinformationaboutourDepartment.

University of CalgaryDepartment of Biological SciencesFaculty of ScienceCorrespondent:VaninaZaremberg

TheBiologicalSciencesDepartmentattheUniversityofCalgary is currentlyorganized in fourclustersbasedongeneral research and teaching interests. They includeBiochemistry, Microbiology, Cell Development &Physiology,andEcology&EvolutionaryBiology.

During this year, several colleagues from BiochemistryhavebeendevotedtoserviceinourDepartment.Elmar PrennerandGreg MoorheadcontinuedintheirrolesofAssociateDepartmentHeadforResearchandPlanning,andGraduateProgramrespectively.Ken NgandVanina Zaremberg continued as chairs of the BiochemistryclusterandBiochemistryprogramrespectively.

It has been a prosperous year for our cluster in bothresearchandteachingactivities.Manyofourmembershavebeeninvolvedinthedevelopmentofmultidisciplinaryinitiatives, have secured important sources of funding,andhavereceivedprestigiousrecognition.Ourtraineesarethedriving forceofourResearchprogramsandweare proud of their accomplishments. Several graduatestudents have finalized their degrees and have beenrecognized with distinctions/awards for their excellentresearch and teaching achievements. These are thehighlightsoftheyear:

On the research side, Marie Fraser’s group continuesto appreciate remote access to the macromolecularcrystallographybeamlinesattheCanadianLightSource.M.Sc.studentJinhongHureliedonthisaccesstoshowhow thewell-known inhibitor fromGarcinia cambogiabindstotheenzymeATP-citratelyase.GraduatestudentsKyle McDade and Vinh Nguyen were both awardedQueen Elizabeth II Scholarships – they are still seekingdiffraction-qualitycrystals.

Ian Lewis’ research group had an exciting year. Themain highlight was the launch of a new international

collaborativeefforttocombatthegrowingglobalburdenof infectious diseases using a new Precision InfectionManagement (PIM) approach. This new strategyharnesses state-of-the-art diagnostic tools to enableclinicians to identify dangerous infections before theyprogress into life threatening infections andtitrate thelevelofclinical interventionaccordingtoeachpatient’srisk profile. The new approach will help minimize theoveralluseofantibioticsandwillallowmoreaggressivetherapyforthosepatientswhoareatthemostrisk.Theinternational team working on these efforts includesfellowBiologicalSciencescolleagueSergei Noskovandisco-ledbyDeirdre Church,whoearnedherPh.D.fromtheBiologicalSciencesdepartmentin1985andiscurrentlyaProfessorintheCummingSchoolofMedicine.TheefforthasbeendesignatedbyAlbertaHealthServicesasoneof the province’s key Precision Health DemonstrationProjects, and is supported by Genome Canada, CIHR,ComputeCanada,theBroadInstitute,andHarvardPublicHealth.

Sergei Noskov’s groupwelcomed two graduate studentsthis year (Mirna Damergi and Shudipto Kazi Amin) tocontinue projects on selective transport across cellularmembranes. The modelling of biochemical phenomenafromproteintocellularlevelremainedthemajorfocusofallresearchactivitiesintheNoskovlab.Peter Tieleman, Sergei Noskov andJustinMacCallum(Chemistry)wereawardedanNSERC-RTIgranttobuildastate-of-the-artsuper-computercluster for applications ranging from protein interfacedesign to systems biology. The computational platformlaunched in 2018will provide direct support toGenomeCanadaLargeScaleAppliedResearchProjectsaspartoftheAntibioticResistanceDatabaseeffort.JohnKeenanFanninghas successfully defended his M.Sc. thesis on molecularmechanisms controlling calcium-induced conformationaldynamicsinl-plastin.

Elmar PrennercontinuedhisteachingintheNanoscienceminor and Biochemistry programs. His basic scienceresearchfocusesonlipid-metalinteractions,lipid-basedanticancerdrugs andnanoparticle-baseddrugdelivery.His applied research, which deals with the design offluorescence instruments and bioanalytical assays, hasmoved into commercialization. Elmar serves on theeditorialboardofBBABiomembranes.

Dae-Kyun Ro was awarded an Alberta Innovate Granttoinvestigategenomeeditinginpea(Pisumsativum)to


improvetheflavourqualityinpeaflour.HewasinvitedtoYangtzeUniversity,China,asavisitingprofessorforguestlecturesstartingin2018.

TheCentre forMolecularSimulation,directedbyPeter Tieleman, organized several well-attended seminarsby visiting speakers. The Tieleman group developscomputer models to study lipids and membraneproteins, at both the atomistic level and at a slightlycoarserlevelofdetail,inthenowwidely-usedMARTINIforcefieldforbiomolecularsimulation.Workingtowardshigh-throughputcomputationalscreeningofinteractionsbetweenlipidsandmembraneproteins,theycontinuetodevelopnewtoolsformembraneproteinsimulationsandapplications to ABC transporters and othermembraneproteins.2017wasaparticularlyexcitingyearforhumanABCtransporters,withmanynewstructuresappearingintheliterature,includinglong-awaitedstructuresofCFTR.Thegroupisworkingonseveralcomputationalprojectsin this area. Eduardo Mendez-Villuendas successfullydefended his Ph.D. thesis on lipid-protein interactionsandimplicationsforviralmaturation.

Congratulations go out to Raymond J. Turner for winning a university teaching excellence awardfor graduate supervision. Ray spent ten weeksduring the Fall as a visiting professor in residence, awarded via a cooperative international funding envelope for small sized universities. He spent histime lecturing in graduate Biotechnology coursesand a course on the Biochemistry and Chemistry of Biological Nanomaterials offered between the University of Verona and the University of Venice, Italy.During thistime,hebuilt productivecollaborations which provided his Ph.D. student, Elena Piacenza, with an opportunity to visit and perform experimentsusingsynchrotronbeam lines inGrenoble,France.Thiscame from extending his research on studying the re-sistance mechanisms against metal ion-based antimi-crobials towards using bacteria as biofactories for pro-duction of metal nanomaterials. This line of researchtook off in the Fall of 2017, leading to the productionofTenanorodsof impressivestabilityandsize,withdi-mensionsof~4x20x800nm,as recentlydisseminat-edinScientificReports.Ph.D.studentNatalieGugala inRay’sgroup,whoisevaluatingthebiochemistryofmet-al-based antibiotics, published her novel findings in J.Antibioticsand in Biofouling. Post-doctoral fellowDr. J.Lemire,togetherwithNatalie,hadtheirresearchonthe

biochemistry of silver toxicity and resistance highlighted at the Experimental Biology conference,whichledtoseveralpressreleases.

Vanina Zaremberg wasinvitedasaspeakeratthe2017Gordon Research Conference on Molecular Biology ofLipids held in the U.S., to present foundational workon theestablishmentof signalling lipidpools and theirassociatedmetabolism.Shecurrentlyservesaseditorialboardmember for the Journal of Biological ChemistryandisamemberoftheNSERCevaluationgroup,Genes,CellsandMolecules. Ph.D.studentSuriaGanesanfromthe Zaremberg lab was the recipient of an Eyes HighInternational Doctoral Scholarship awarded by theUniversityofCalgary.Suriacontributedtoahigh-qualitypaper in collaboration with Dr. M. Terebiznik’s group(Uof Toronto)published in the JournalofCell Biology. TheworkwashighlightedintheJCB“Spotlight”section.Brittney Shabits from the same group received aQE-IIgraduatescholarshipandbrilliantlydefendedherM.Sc.thesis. The group welcomed newM.Sc. student LauraSosa,whohasinitiatedexcitingworkontheroleoflipidmetabolismandtelomeresilencingincollaborationwithDr.JenniferCobb(CummingSchoolofMedicine).LaurawasawardedaQE-IIgraduatescholarship.

On the Teaching side, Isabelle Barrette-Ng launchedProgram SAGES (SoTL Advancing Graduate Educationin STEM) using funding from the University of CalgaryTeachingScholarsProgramand theGraduateStudents’AssociationQualityMoney Program. SAGES consists oftwo credit courses that help STEM graduate studentsdevelopanevidence-based,reflectiveteachingpractice.The first course consists of a survey of the theory ofteaching and learning of STEM at the post-secondarylevel.Thesecondcourseconsistsofateachingpracticum.14graduatestudentsfromacrosstheFacultyofSciencecompletedtheprogramin2017andpresentedtheresultsoftheirpracticumatourfirstannualSAGESCelebrationof Teaching and Learning event on June 29, 2017.For her work on SAGES and other programs, Isabellewas awarded the 2017 Faculty of Science EducationalLeadershipaward.

Elke Lohmeier-Vogel continued teaching andcoordinating in three biochemistry laboratory coursesintheFallandWinterterms,aswellasanintroductorybiology course. She was nominated for a teachingexcellence award in BCEM 403. Over the summer of


2017, sheworkedwith the iGEM team alongwith hercolleagueMayi Arcellana-Panlilio toassistthestudentsintheirresearchproject,whichtheypresentannuallyinBostoninaglobalcompetition.ElkeandMayipresentedateachingworkshopattheannualUniversityofCalgaryPost-secondary Learning and Teaching Conference inMay,ontheinterestingprocessbywhichstudentsintheiGEMteamsselectatopictoworkonfortheyear.

University of GuelphDepartment of Molecular and Cellular BiologyCorrespondent:FrancesSharom

Faculty news:Dr. Emma Allen-Vercoe was awarded a ResearchLeadership Chair, a new3- to 5-year internal award torecognize research excellence and innovation. Theawardsarebasedonscholarlyoutput,research-relatedknowledge mobilization, research-derived innovationandtrainingofhighlyqualifiedpersonnel,andrecognizeresearcherswhoseresearchsuccessesalreadysetthemapartfromcolleaguesintheirdisciplinesglobally.Awardwinners will present their work to the university andthewiderGuelph community through special researchevents.

Dr.EmmaAllen-Vercoe

Dr. Jim Uniacke received4 yearsof funding fromCIHRtolookattargetedtreatmentofhypoxic,orlowoxygen,tumourregions.Heplanstousemodelcancercelllinesandnanoparticlestodelivergeneticmaterialtohypoxichumantumoursgraftedontomice.Dr.Uniacke’sresearchteam aims to learn how hypoxic cancer cells makethe proteins they need to survive and spread. These

mechanisms could then be targeted in cancer therapytoimpairtheabilityofacancercelltomakethetoolsitrequires,essentiallydisarmingthecell.Jim’slabwasalsoselectedasGuelphCo-opEmployeroftheYear.

CongratulationsgotothefollowingMCBfacultymembersforsuccessfully renewing theirNSERCDiscoveryGrantsin2017:Joseph Colasanti, Marc Coppolino, Nina Jones (whoalsoreceivedanAcceleratorgrant),David Josephy andJanet Wood.

SeveralMCBfacultymembersparticipatedinsuccessfulNSERC group applications for new instruments andinfrastructure in2017.Steffen Graether (co-applicants:Leonid Brown (Physics), George Harauz, Rod Merrill, Stephen Seah, Janet Wood and Cezar Khursigara)acquired ITC and DSC systems as part of a ProteinKnowledge Suite. A Zebrafish Advanced Life SupportSystemwasawarded toTerry Van Raay (co-applicants:NickBernier(IntegrativeBiology),Scott Ryan,GlenVanDer Kraak (Integrative Biology), John Dawson, ToddGillis (Integrative Biology) and Niel Karrow (AnimalBiosciences)). Doug Goff from Food Science (co-applicants: Emma Allen-Vercoe, Nina Jones, Cezar Khursigara, and Chris Whitfield) was awarded a cryo-preparationunitforaScanningElectronMicroscope.

InMay,Drs. Nina Jones andLucy Mutharia werehonouredas members of a group of 30 Women of Distinctionchosen by the Guelph YMCA-YWCA for their lifetimecontribution toSTEM (science, technology,engineeringandmath)andeducation,trainingandmentorship.

New faculty appointments:Three new faculty members joined our departmentduring2017.

Dr. Melissa Perreault, a neuroscientist with expertisein electrophysiology, cell signalling and behaviouralneuroscience using animal models of neuropsychiatricdisorders and neurodegenerative disease joined theDepartment as anAssistant Professor in January 2017.Dr. Perreault’s scientific research career began as anundergraduate project student in the laboratory of Dr.C. David Rollo, an evolutionary biologist at McMasterUniversity who studied evolutionary theory based onintegratedlifehistorytrade-offs.SheremainedinhislabforanadditionaltwoyearsandaftercompletingherM.Sc.degree,pursueddoctoralresearchunderthesupervision


ofDr.HenrySzechtmanintheDepartmentofPsychiatryand Behavioural Neuroscience, where her studiesfocussedonopioid-dopamineinteractionsusingananimalmodel system of obsessive-compulsive disorder. Dr.Perreaultcontinuedherresearchaspost-doctoralfellowin the laboratoryofDr. SusanGeorgeat theUniversityofToronto,amolecularpharmacologistwhoseresearchfocussed on the dopamine D1-D2 receptor complexand its role in addiction and schizophrenia.Duringherpost-doctoral studies she spent a month in Tuscany,Italy at theNeuroscienceSchool forAdvancedStudies,where she had the opportunity to meet Dr. AnthonyGrace, Distinguished Professor of Neuroscience at theUniversityofPittsburgh.Duringherpost-doctoralstudiesshereceivedtraininginDr.Grace’slaboratorywhereshelearnedhowtorecordandanalyzeneuronaloscillationsin awake, freely moving animals. These oscillations,which represent the summed electrical activity fromnumerous neurons, have emerged as being critical tothe neuropathology of a number of CNS diseases. AttheUniversityofGuelph,Dr. Perreaultwill continue tocombinecellandsystemsresearchwithanimalbehaviourto help gain insights into the mechanisms of disease,

withaparticularfocusondepression, schizophreniaand Alzheimer’s disease.She is also excitedabout being part of therecently implementedNeuroscience major atthe University of Guelph,and looks forward toparticipatingincurriculumdevelopmentforthisnewprogram.

AssistantProfessorDr.MelissaPerreault

Dr. Georgina Cox joinedtheDepartmentasanAssistantProfessoronJuly1,2017.GeorginacompletedherPh.D.attheUniversityofLeeds,U.K.,whereshefirstbecamefascinated with antibiotic resistance and the intricatemechanisms bacteria have evolved to circumvent theinhibitory action of these small molecules. FollowingcompletionofherPh.D.,Georginajoinedthelaboratoryof Dr. Gerry Wright within the Institute of InfectiousDisease Research (IIDR) at McMaster University. Herpost-doctoralresearchbuiltuponherexistingskillsbase,involving the structural andmolecular characterization

of antibiotic resistancemechanisms, and also exposedher to cutting edge drug discovery campaigns andtheworldofnaturalproducts.Georgina is settinguparesearch program studying host-pathogen interactionsandbacterialantibioticresistance,andlooksforwardtoparticipating in the delivery of undergraduate coursesin Microbiology and Biochemistry. Utilizing a mixture

of structural, molecularand genetic approaches,researchinherlabinvolvesgaining insight into twoareas: how bacteriaresistantibioticsandhowthey interact with theirhost. The over-archinggoal of her research isto identify and developinnovativealternativestotraditional antibacterialchemotherapy.

AssistantProfessorDr.GeorginaCox

Dr. Jasmin Lalonde, whohasinterdisciplinaryexpertisein neurobiology and biological psychiatry, joined thedepartment as anAssistantProfessor inAugust 2017.Jasmin completed his undergraduate studies at theUniversity of Ottawa in 1999. He thenmoved toMc-GillUniversitywherehecompletedaMaster’sdegreeandPh.D. in theDepartmentofPsychology.Asadoc-toralstudentinthelaboratoryofDr.AviChaudhuri,Dr.Lalonde initiated a seriesof studies that revealedun-suspectedregulationofthecalcium/calmodulin-depen-dentproteinkinaseIV(CaMKIV)andthecAMPresponseelement-bindingprotein (CREB) transcription factor inneuronsubtypesofthemonkeyprimaryvisualcortex.In2007,Dr.LalondejoinedthelaboratoryofDr.GraceGill at Tufts University School of Medicine as a CIHRPost-doctoral Fellowwhere he studied the regulationandfunctionoftranscriptionfactorSpecificityprotein4(Sp4)inneuronalculturesandageneticSp4mousemod-el. While trying to understand which calcium-depen-dentsignaltransductionpathwayparticipatesincontrolofSp4proteinstability,hemadestrikingobservationsshowingthatSTIM1-mediatedStore-OperatedCalciumEntry (SOCE)playsa central role in thisprocesswhenneuronsareatrest.HisfindingsonneuronalSOCEwerepublishedinScience Signaling.AsDr.Lalonde’sworkonSp4andSOCEwasreaching itscompletion,hewas in-


vitedtojointhelaboratoryofDr.StephenHaggartyattheMassachusettsGeneralHospital (MGH).There,hegainedadditionalexperiencewithneuropharmacology,translationalneuroscienceandstemcellbiology,aswellas high-throughput screening techniques. Among hismanyaccomplishmentsatMGH,Dr.LalondefoundthatacetylationofaspecificlysineresidueofActivity-regu-latedcytoskeleton-associatedprotein(Arc)canpreventtheubiquitin-proteasomesystemofdegradingthiskeyeffector of synaptic plasticity and long-term memoryconsolidation.ThisworkwasrecentlypublishedinNa-tureCommunications.HisrecentCIHR-fundedpost-doc-toralinvestigationintothemolecularbasisofstore-op-eratedcalciumentryinbipolardisorderwasrecognizedwitha2016YoungInvestigatorGrantfromtheBrain&Behavior Research Foundation (formerly NARSAD) intheU.S.,which currently supports research in his labthatexamines thepossible connectionbetweenSOCEdysfunctionandbipolardisorderpathophysiologyusing

patient-derived inducedpluripotentstemcells.AttheUniversityofGuelph,Dr. Lalonde is establish-ing a research programexamining themolecularmechanismsthatcontrolneuronal function, andhow these contributeto the pathophysiologyof bipolar disorder andschizophrenia.

AssistantProfessorDr.JasminLalonde

Introducing the G. Magnotta Lyme Disease Research Lab:In June, 2017, the College of Biological Sciences atthe University of Guelph was thrilled to announce apartnershipwiththeG.MagnottaFoundationforVector-Borne Diseases to establish a dedicated Lyme diseaseresearchlabintheDepartmentofMolecularandCellularBiology. Lyme is a debilitating tick-borne zoonosis thatis incompletely characterized, and poses an escalatingthreattothehealthofCanadians.NamedinhonourofthelatevintnerandavidoutdoorsmanGabeMagnotta,who died from complications of Lyme disease, thenew lab is harnessing a multidisciplinary approach touncover disease mechanisms and ultimately improvediagnostics and treatment strategies. Led by a cell-

signallingbiochemist,Dr. Melanie Wills,thelabbenefitsfrom departmental strengths in microbiology, proteinchemistry,andcellularpathologytosupportaresearchprogrammerevolvingaroundmicrobialcharacterization,host-pathogen interaction, and human diseasedeterminants.Aclinical-academicpipelineiscurrentlyindevelopmenttosupport thispatient-orientedresearch.TheG.MagnottaLabisalsocentraltoalargerinitiativethatunitesresearchnodesacrossthecountrytoaddressthe full complexityofLymedisease, from itsecologicalunderpinnings to healthpolicy and practice.The Canadian LymeConsortium is expectedtomake its public debutinthesummerof2018.

Dr.MelanieWills,DirectoroftheG.MagnottaLymeDisease Research Lab

TheMagnottalabteamatwork

Retirements:Faculty retirements continued in 2017, with Dr. Peter Krell retiring in February,Dr. Joe Lam in June, andDr. Janet WoodinAugust.Allthreearenowwindingdowntheir research activities after distinguished careers inbothresearchandteachingattheuniversityovermanydecades.

Staff news, comings and goings:Dr. Paula Russell wasselectedasarecipientofthisyear’sPresident’s Award for Exemplary Staff Service in thecategoryofHiddenHero.ThisawardrecognizedPaula’scontributions to our Department and the Universityin running the senior undergraduate laboratories


in Analytical Biochemistry and Enzymology. We allappreciatedherwillingnesstoprovideexcellentbehind-the-scenes support to our students, faculty, and staff.PaulaleftthedepartmentinSeptember2017forHealthCanadainOttawa;wewishherwellinhernewposition.

Dr. Colin Cooper replacedPaulaRussellasUndergraduateTeachingCoordinatorinNovember2017.HeobtainedhisB.Sc.andM.Sc.inCellBiologyandGeneticsfromWesternUniversityandhisPh.D.inBiochemistryandMicrobiologyfrom McMaster University. Engaging students in theactive learningenvironmentof the laboratory isColin’sprimary focus, with the goal of giving each student arewardingstarttotheirbiochemistrycareer.

Graduate student awards:David Sycantha (Clarke lab) and Danielle Williams (Whitfield lab) both received awards at the CanadianSocietyofMicrobiologistsConferenceheld inWaterlooinJune2017.DavidwontheStudentSymposiumAwardFor Top Student Oral Presentation, and Danielle wastherecipientoftheTerryBeveridgePosterCompetitionAward.

Our graduate students wonmultiple poster awards atthe 2017 Waterloo-Guelph-Laurier 3rd Annual ProteinSymposium,whichwasheld in JuneandhostedbytheUniversity of Waterloo. Twenty-one excellent postersand3shorttalkswerepresentedbyMCBstudentsandresearch staff.Congratulations to theaward recipients:Liam Doyle(Whitfieldlab),Carys Jones(Clarkelab),Sean Liston(Whitfieldlab)andKevin Rea(Akhtarlab).

University of LethbridgeCorrespondent:UteKothe

Faculty news:Dr. Ute Kothe,anassociateprofessorintheDepartmentofChemistryandBiochemistry,hasbeenwelcomedbytheRoyalSocietyofCanadaasoneof70newmemberstoTheCollegeofNewScholars,ArtistsandScientists.

Dr. Athanasios ZovoilishasbeennamedaTierIICanadaResearchChairinRNABioinformaticsandGenomics.Dr.A.Zovoilis,abioinformaticianandgenomicist,cametotheU of Lethbridge fromBoston’s HarvardUniversityto establish and pursue a research program aimed atdeveloping personalized treatments for diseases like

cancer and dementia. He is amember of the AlbertaRNAResearchandTrainingInstitute(ARRTI).AcollaborationbetweenDrs. Athanasios ZovoilisandMajid Mohajerani toinvestigatemolecularmechanismsinvolved inAlzheimer’s disease has received fundingby the Alberta Prion Research Institute. The tworesearchers are professors of bioinformatics inthe Departments of Chemistry and Biochemistry,and Neuroscience, respectively, and combine theircomplementaryexpertiseingenomics,bioinformaticsandanimalstudiesinaninterdisciplinarystudy.

Dr. Wade Abbott ofAgricultureandAgri-FoodCanadaandhisteamhavepublishedaresearchstudyonthedegradationofdietarypecticglycansinhumancolonicBacteroidesinNatureMicrobiology.Thestudycreatesopportunities to manipulate the microbiome andpossiblyenhancefooddigestibility.

ThepioneeringworkbythehighschooliGEMprogramhas been featured in Nature Biotechnology. Thearticle, co-authored by Drs. Hans-Joachim Wieden andBrian Dempsey of theDepartmentof Chemistryand Biochemistry and their coworkers, describes “Asyntheticbiologyapproachto integrativehighschoolSTEMtraining”.

The U of Lethbridge iGEM teams are succeeding at all levels:For several years, the University of Lethbridge hasbeentheproudhomeofbothacollegiateiGEMteamcomprising graduate and undergraduate students,aswell as a high-school iGEM team. Both teams arecompetingintheinternationalGeneticallyEngineeredMachines (iGEM) competition taking place eachNovember in Boston, Massachusetts, USA. In 2017,bothteamswereonceagainhighlysuccessful.TheUofLethbridgehighschool teamwasawardedasilvermedalandthecollegiateteamagoldmedal,andalsoreceived nominations in three special categories,including Best Software, Best Education and PublicEngagement, and Best Integrated Human Practices.In addition, the team received the Biosafety andBiosecurityCommendation.

“This year, it’s safe to say the U of L team was thehighest-achievingCanadianteamatthisinternationalcompetition,” says Dr. Hans-Joachim Wieden, aprofessor in the Department of Chemistry and


Biochemistryandteamadvisor.“Iamextremelyproudofour students. Theyworkedhardand these resultsprove their efforts were on themark.What’smore,the Federal Bureau of Investigation (FBI), in theirpresentationatthejamboree,mentionedtheUofL’sworkasapositiveexample.”

The collegiate team focused this year on makingsynthetic biology safe and available for everyone.Specifically, the team was trying to develop a cell-freesyntheticbiologysystemtobringthistechnologyto as many people as possible, and make surethat it’s democratically spread out. Then the teamrealizedthatthistool,asusefulasitis,alsoopensupunforeseen biosecurity risks. Following the Biosafetyand Biosecurity Commendation after the GiantJamboree 2017, one of the team members and anM.Sc.studentattheUofLethbridge,Chris Isaac, was chosen to be one of five student participants in theiGEMFoundation’sdelegationtotheMeetingofStatesPartiestotheBiologicalWeaponsConvention(BWC)inGenevainDecember2017.

The high school iGEM team worked towards thedevelopment of biological pigment for use in themanufacturing of ink to mitigate the environmentalconsequences of traditional ink manufacturing. Thehigh school teammemberswrote apaper about thedesignoftheirprojectandsubmittedittoBiotreks,anon-line journal for high school students. After beingjudgedbymembersofthesyntheticbiologycommunity,theLethbridgeteamwasgivenanEducationAwardtoacknowledgetheiroutstanding job incommunicatingtheirknowledgeandtechniquestotheirpeers,andanawardforvisualcommunicationfortheiruseoftablesand figures to augment their work. Moreover, theteamwasawardedBestCommunicationattheAlbertacompetitioninJune2017.

Gairdner Awardee Dr. Lewis Kay visits U of Lethbridge:TheDepartmentofChemistryandBiochemistryattheUofLethbridgehasonceagainbeenselectedby theGairdner Foundation to host one of the world-classGairdnerAwardees,Dr.LewisKayfromtheUniversityofToronto.Dr.Kay’svisitwasaspecialeventbecausehisresearchinthefieldofbiomolecularnuclearmagneticresonance(NMR)spectroscopyisofhighinteresttoallresearchers in thedepartment, frombiochemistry tochemistry.Accordingly,thevisitwasjointlyorganized

by the Alberta RNA Research and Training Institute(ARRTI)aswellastheCanadianCentreofResearchinAdvancedFluorineTechnologies(C-CRAFT).Everybodyon campus was truly inspired by Dr. Kay’s scientificlecture presenting his impressive studies of the p97MolecularMachine.Importantly,Dr.Kayalsoengagedlocal youth by visiting a high school in Lethbridgefor a dedicated lecture that was followed by a longquestionperiod.Dr.Kaycontinuestobeaninspirationfor the undergraduate and graduate students at theUniversityof Lethbridge.He took the time to closelyengagewithstudentsintwodedicatedcareerlunches.Moreover, Dr. Kay attended the concomitant annualChinook Symposium for Chemistry and Biochemistrywhere he talked with many students about theirresearchprojects.

Two Public Professor Lectures from the Department of Chemistry and Biochemistry:The Faculty of Arts and Science has created a verypopular Public Professor Lecture series whereUniversity of Lethbridge professors engage with thelocalcommunity.In2017,nolessthantwoprofessorsfromtheDepartmentofChemistryandBiochemistrywere selected to present their research. In March2017,Dr. Stacey Wetmoretalkedabout“DNADamage,Repair and Disease: How Computers Can Help UsUnderstand”.Inaone-hourlecture,shefascinatedtheaudiencewithanimpressiverangeoftopicsfrombasicchemistry to advanced computational research andapplications in medicine such as cancer treatment.Thelargenumberofquestionsafterherpresentationclearly showedhowmuchDr.Wetmore engaged theaudience. In September 2017, Dr. Ute Kothe thenfollowed the example of her colleague in her PublicProfessor Lecture entitled “From the beginnings ofLife to Modern Medicine: Why RNA Matters”. Byrepresenting the Alberta RNA Research and TrainingInstitute (ARRTI), Dr. Kothe highlighted severalapplications of RNA research from biotechnologyincluding the newest uses of CRISPR systems to theunderstandingof rarediseases and the treatmentofdiseasessuchasspinalmuscularatrophy.BothPublicProfessor Lectures were attended by hundreds ofcommunitymembers,leavingalastingimpact.


University of ManitobaDepartment of Biochemistry and Medical Genetics, Rady Faculty of Health SciencesCorrespondent:LouiseSimard

2017 witnessed the inaugural class of M.Sc. GeneticCounselling trainees. This has been a busy yearwith amix of formal coursework, clinical rotations and thedevelopment of their graduate thesis topics. RachelleDinchongcametouswithanHonoursB.Sc.degreewithHigh Distinction from the University of Toronto. Hergraduate thesis topic is “Mitigating the psychosocialimpact of a false positive newborn screen for inbornerrors of metabolism”. Angela, native to Winnipeg,enteredtheprogramwithaB.Sc.inGeneticsandanM.Sc.inBiochemistryandMedicalGeneticsat theUniversityofManitoba. Her graduate thesis topic is “ExplorationoftheGeneticAssistantPositionintheGeneticsClinic”.AshleighHansencameintotheprogramwithaB.Sc. inMicrobiologyfromtheUniversityofVictoria.Hergraduatethesis topic is “Exploring immigrants’ perceptions ofgenetic counselling: A case study”. Angela Krutish wastherecipientofaManitobaGraduateStudentFellowship,while Rachelle Dinchong was awarded a University ofManitobaGraduateScholarship.

AngelaKrutish,AshleighHansen,andRachelleDinchong(fromlefttoright)posingwithRusty,thetherapydog

Additionally,2017markedanumberofpivotalmilestonesfor Dr. Tamra Werbowetski-Ogilvie,whowas recruitedto our department and the Regenerative MedicinePrograminNovember2010.Thisyear,Dr.Werbowetski-Ogilvieachievedtenure,andwaspromotedtotherankof Associate Professor. Evidence in support of these

achievements included the national recognition shereceived through the renewal of her Tier II CanadaResearchChairinNeuro-oncologyandHumanStemCellswhichcommenced inJuly2017andrunstoJune2022.Furthermore,Dr.Werbowetski-Ogilvie became thefirstManitoban,andoneofthefewCanadians,tobeawardedanAlex’sLemonadeStandFoundationInnovationgrant.Thisisa2year~$249KU.S.awardtostudytheroleofOTX2-semaphoringenesignallingpathwaysinhighlyaggressivemedulloblastomas.Partofthisworkwaspilotedby2017CIHR Project Grant Bridge funding (April-Sept 2017).Together,thishasallowedhertorecruittwonewpost-doctoral fellows, Drs. Jamie Zagozewski (Ph.D. traineeofDr.DavidEisenstat), andBrentGuppy (Ph.D. traineeofDr.KirkMcManus).Dr.Zagozewskiwastherecipientof a post-doctoral fellowship from the partnership ofResearch Manitoba, the Children’s Hospital ResearchInstituteofManitoba,andCancerCareManitoba(2017-2019).WelookforwardtofollowingJamie’sandBrent’s

progress in understandingmedulloblastomapathobiologyand potential combinatorialtherapeutic modalities in thecomingyears.Finally,Dr.TamraWerbowetski-Ogilvie was oneof the 2017 nominees forthe YMCA/YWCA Women ofDistinctionAward.

Dr.TamraWerbowetski-Ogilvie

Other facultymemberswere also successful in attractingresearch funding despite the current exceedinglycompetitiveandchallengingenvironment;consequently,itisdoublyimportanttocelebratethesesuccesses.FundingwasattractedfromawidevarietyoforganizationsthatincludetheCanadianStatisticalSciencesInstitute(Dr. Pingzhao Hu as Co-investigator), Cancer Research Society (Drs. Mark Nachtigal and Kirk McManus), CancerCare ManitobaFoundation (Dr. Kirk McManus), Children’s HospitalResearchInstituteofManitoba(Drs. Pingzhao Hu, Barbara Triggs-Raine), Canadian InstitutesofHealthResearch (Dr. Tamra Werbowetski-Ogilvie),CanadaResearchChairs(Dr. Tamra Werbowetski-Ogilvie),DiagnosticServicesManitoba(Drs. Mark Nachtigal andKirk McManus),Glyconet (Drs. Gilbert Arthur, Brian Mark and Barbara Triggs-Raine),HeartandStrokeFoundationofCanada(Dr. Jeffrey Wigle),LeukemiaandLymphomaSocietyofCanada (Dr. Spencer


Gibson), NSERC (Drs. Jim Davie, Barbara Triggs-Raine),ResearchManitoba(Drs. Hao DingandTrevor Pemberton),St. Boniface Hospital Foundation (Dr. Jeffrey Wigle), andthe Western Canadian Universities, Collaborative ProjectSeed Funding (Dr. Pingzhao Hu). Dr. Hu was also a Co-investigator on a five-year NSERC CREATE Program grantawardof$1.65milliondollars tosupport the“Visualandautomateddiseaseanalytics (VADA)” trainingexperience.Dr. Leigh MurphyisaCo-investigatorofarecentlyfunded“Investigator Initiated Research Scheme” by theNationalBreastCancerFoundation inAustralia,a>1milliondollarAustralian-Canadianinitiativethatseekstouse“proteomicsto transform treatment decisions for breast cancer”. AnimportantcomponentofthisinitiativewillbetheCanadianBreast Cancer Tissue Bank. Collectively, this funding willadvanceourresearchprograms,andprovidecriticalsupporttoourtrainees.

Thedepartmentisbuiltupontheproductivityofitstraineesand fed by our graduate program. This year, Ifeoluwa Adwewumi (Dr. Jim Davie), Yasamin Asbaghi (Dr. KirkMcManus), Anna Blankstein (Dr. Spencer Gibson), Chi Chen(Dr.PingzhaoHu),Lexi Ciapala(Dr.SpencerGibson),Miriam Derksen (Dr.SpencerGibson),Veronica Lau(Dr.JimDavie),andMargaret Stromecki (Dr.TamraWerbowetski-Ogilvie) defended their theses, and their M.Sc. degreeswereconferred.TwostudentsreceivedtheirPh.D.degrees,Alexandra KuzykandSanzida Jahan,undertheguidanceofDrs.SabineMaiandJimDavie,respectively.

The quality of our graduate students was recognizedby a number of awards. Ph.D. candidate Lisa Liang (Dr.TamraWerbowetski-Ogilvie)wasawardedtheSheuL.LeeFamily Scholarship in Oncology Research and theNancieJ Mauro Graduate Scholarship in Oncology Research.Ph.D. candidate Sasha Blant (Dr. Trevor Pemberton)was the recipient of two very prestigious University andDepartmental awards, namely, the President’s GraduateScholarshipinHumanGeneticsandthePhyllisJ.McAlpineGraduate Fellowship, respectively. Research Manitobagraduate student fellowships were awarded to Fadumo Osman (Dr.JimDavie)and Amandeep Singh (Dr.SpencerGibson).Amandeep SinghwasalsoarecipientofaMastersNSERCCanadaGraduateScholarship.Onthepost-doctoralfront,Dr. Svetlana Frenkel(Dr.PingzhaoHu)wasrecognizedfor her “Poster of Distinction” at the recent AmericanGastroenterological Association Digestive Disease Week.This distinction underscores the fact that her work wasratedinthetop10%ofallAGAabstractsselectedforposter

presentation.Finally,ourstudentshighlighttheirresearchprogress at the departmental Seminar Series and everyyearwewitnessawiderangeoftopicsthattranscendmanydisciplines.One strikingexample this yearwasanumberofpresentationsoutlining theuseofmachine learningtobetter our understanding of cancer. At the end of eachcycle, graduate trainees vote for the most outstandingOral Presentations, and in 2017 the top three awardswenttoMargaret Stromecki (M.Sc.traineewithDr.TamraWerbowetski-Ogilvie),Laura Thompson(Ph.D.traineewithDr. KirkMcManus) andChen Chi (M.Sc. traineewith Dr.PingzhaoHu).

Nottobeoutshonebyourtrainees,facultywerealsoatthereceivingendofseveralimportantawards.Congratulationsgo toDr. Jim Davie, who was the Canadians for HealthResearch“Researcherof theMonth” thispastApril2017and Dr. Kirk McManus, who received the “Scientists’Choice Award” for the 2016 Best Drug Discovery &Development Article of the Year entitled “Identificationand characterization of cancer risk factors using highthroughputcellscreening”.Dr. Cheryl Rockman-Greenberg continues to receive accolades, and this year was giventhe 2017 Founders Award in recognition of outstandingcontributionstoClinicalGeneticsandMetabolicDisorders,andanoutstandingcareer inMedicalGenetics inCanadaandabroad.

University of TorontoDepartment of BiochemistryCorrespondent:AlexPalazzo

Faculty news:Move to MaRSInJanuary2018,wecompletedthesecondstageofthemovefromtheMedicalSciencesBuildingtothe15thand16thfloorsof theMaRSWestDiscovery tower, locatedon the southeast corner of University Avenue andCollegeStreet.Overall,14ofthecorefacultymembershavemoved,andwerejoinedbytwonewrecruits,HaleyWyatt and KarenMaxwell. In spring 2018, a third newfacultymember,Dr.KateLeeisslatedtosetuphernewlabintheremainingspotonthe15thfloor.

ProfessorJustinNodwellwasreappointedforanother5years as chair of theBiochemistryDepartment.Duringhisfirstterm,Dr.Nodwellplayedaninstrumentalroleininitiating and implementing themove toMaRS, hiring


four new tenure-streamand one non-tenure-streamcore faculty members,introducingarotationsystemfor the incoming graduatestudents, revamping theBiochemistry website andstarting an annual retreatfortheDepartment.Besidesall of this, he was recentlyelected as a Fellow of theAmerican Academy ofMicrobiology.

Faculty awards:Thispastyear,Dr. Lewis KaywasawardedtheGairdnerInternational Award, Canada’s highest science prize.Dr. Kay’sworkon thedevelopment anduseofnuclearmagneticresonance(NMR)techniquesfor investigatingmolecularmotionandshort-livedconformationsinlarge

multiprotein complexes,has pushed boundaries andopened up new paradigmsinmacromolecularstructureand function. He was alsonamed an Officer of theOrderofCanada,oneofourcountry’s highest civilianhonours, which recognizesoutstanding achievement,dedicationtothecommunityandservicetothenation.

Dr.LewisKay

Dr. Sergio Grinstein was selected by the CanadianSociety for Molecular Biosciences as the recipient ofthe Canadian Science Publishing Senior Investigator

Award for 2017. Dr. Grinstein has contributed manyseminalfindingstothefieldsofcellbiology,physiologyand immunity, particularly on phagocytosis and host-pathogeninteractions.HiscontributionsincludestudiesontheV-ATPaseandNADPHoxidaseinneutrophils,theregulation of cytosolic and organellar pH, membranedynamics and signalling required for phagocytosis, thespatialorganizationandsignallingofscavengerreceptors.Hepresenteda talkat theCSMBmeeting inOttawa inMay2017.

Dr. Charlie Deber received the 2017 Bruce MerrifieldAwardoftheAmericanPeptideSociety.ThisAwardwascreated in 1997 in honour of Dr. R. Bruce Merrifield,whowon theNobelPrize inChemistry in1984 for theinvention of solid phase peptide synthesis. The awardispresentedeverytwoyearstoleadersinthefieldwhohavedemonstratedoutstandingcareeraccomplishmentsin peptide research, “recognizing the highest level ofscientificcreativity”.Dr.Deber’sresearchfocussesonthehierarchyof forcesthatcharacterizethe interactionsofpeptidesandproteinswithmembranes,andhowtheseforcesproducemembraneproteinstructureandfunction.TheawardwaspresentedtoDr.Deberandco-recipientDr.RobertHodges,oftheUniversityofColorado,atthe25thAmericanPeptideSymposium inWhistler,B.C.onJune,2017.

Dr. Scott Prosser received the 2017 Jeremy KnowlesAwardoftheRoyalSocietyofChemistryfor“successfulapplication of fluorine and multinuclear NMR tounderstand conformational dynamics and allostery inenzymes and G-protein coupled receptors”. The RoyalSocietyofChemistrygivesouttheJeremyKnowlesAwardtorecognizeandpromotethe importanceof inter-andmultidisciplinary research between chemistry and thelifesciences.

Dr. Greg FairnhadastellaryearashewontheWalterA.ShawYoungInvestigatorAwardinLipidResearchfromtheAmericanSocietyforBiochemistryandMolecularBiologyandwasappointedtotheeditorialboardofthejournalsScientificReports,Traffic,andCellular Microbiology. Dr. Fairnalsoco-organizedthe2017CSMBAnnualMeetinginOttawa.

The department also congratulates Dr. Stavroula Andreopoulos on receiving the 2017 SustainedExcellence and Innovation in Life Sciences Education

A view looking north from the 15th Floor of the MaRSWestDiscoverytower

Dr.JustinNodwell


Award,whichwaspresentedto her on May 15th at the15th Annual EducationAchievement Celebration.This award recognizes andcelebrates the tremendouscontributions being madeto medical teaching andeducation scholarshipthroughout the Faculty ofMedicineattheUniversityofToronto.

Dr.StavroulaAndreopoulos

Other faculty news:Canada Research ChairsThreeBiochemistryfacultymemberswerenamednewCanadaResearchChairsbythefederalgovernmentthispastfall:Haley Wyatt,Tier2CanadaResearchChairinMechanismsofGenomeInstability;Jean-Philippe Julien, Tier2CanadaResearchChairinStructuralImmunology;andTrevor F. Moraes,Tier2CanadaResearchChairinStructuralBiologyofMembraneProteins.

Forthepasttwoyears,ProfessorReinhart Reithmeier hasbeensecondedtotheSchoolofGraduateStudiesasSpecialAdvisortotheDeanforGraduateProfessionalSkillsandEngagement.Reinhartcarriedoutanenvironmentalscan of graduate professional development activitiesat the University of Toronto that is summarized ina report to the Dean (http://www.sgs.utoronto.ca/currentstudents/Pages/GPD-Report---July-2016.aspx). HeestablishedtheInnovationinGraduateProfessionalDevelopment Fund (http://www.sgs.utoronto.ca/currentstudents/Pages/SGS-Innovation-in-Graduate-Professional-Development-Fund.aspx) to help developand support new or expanded Graduate ProfessionalDevelopment (GPD) initiatives by graduate studentsandpost-doctoralfellowsattheUniversityofToronto.

Dr. Reinhart Reithmeier

Celebratingthe10,000PhDsProject

Reinhartalsoinitiatedandledthe10,000PhDsProject,whichusedinternetsearchestodeterminethecurrent(2016)positionsofthe10,886individualswhograduatedfromUofTwithaPh.D.inalldisciplinesfrom2000to2015. An opinion piece was published in UniversityAffairsandtheProjectwasfeaturedinarticlesinNature andScience.Thedatafromthe10,000PhDsProject ispubliclyavailableinaneasytonavigateformatontheSGS web-site (http://www.sgs.utoronto.ca/about/Pages/10,000-PhDs-Project.aspx).Allgraduatestudentsareencouragedtoviewtheemploymentoutcomedatafortheirdisciplinetomakemoreinformedchoicesastotheirpossibleandimaginedcareerpathways.

In addition to all this work, Reinhart is the incomingPresident of the Royal Canadian Institute for Science(https://www.rciscience.ca/), a venerable institutioncreatedbySirSanfordFlemingin1850,whosemissionistobringsciencetothepublic.HisgoalasPresidentistomovetheorganizationbeyondtheboundsofTorontotomakeRCIScienceanationalvoiceforscience.

Research highlights:Visualizing the cellular machinery in virtual reality (NatureMethods201714:1122–1123)TheAutodeskMoleculeViewer,anewtooltovisualizeatomic structures using Virtual Reality (VR) softwarewas developed by a partnership between Aidin Balo,a graduate student in the Ernst lab, and Autodesk,located in the MaRS Discovery district. Their newtool, described in this paper, allows users to easilyimport atomic coordinates, generate structuralrepresentations, annotate in space, store individual3D structural snapshots and share interactive 3D and


immersiveVRstructuralwalkthroughsdirectlyinawebbrowser. This tool has been used at conferences andstructural biology presentations where the audienceusesVRheadsets tosee insideandaround3Datomicstructures.

Single molecule imaging of mRNAs by the Palazzo lab provides new insight into protein synthesis in mammalian cells (CellReports201721:3740–3753)ThePalazzolab,incollaborationwithJeffChao’slabattheFriedrichMiescherInstituteforBiomedicalResearchin Basel, Switzerland, has resolved a long-standingpuzzle inhowcellsusemRNAstosynthesizeproteins.Previously,itwasknownthatmostmRNAsthatencodesecretoryormembrane-boundproteinsarelocalizedtothesurfaceoftheendoplasmicreticulum(ER),a largetubulatedorganellefoundinsideofalleukaryoticcells.By visualizing single mRNA particles, the Palazzo andChao labs demonstrated that a substantial fraction ofmRNAsthatencodecytosolicproteinsarealsolocalizedto the surface of the ER, contrary to most currentmodels. This study adds a new wrinkle to our basicunderstandingofhowproteinsaresynthesizedincells.

Enenkel lab discover how proteasomes reorganize during cellular quiescence(MBoC201728:2479-2491)TheEnenkel labdemonstrated that inquiescent cells,proteasomes, the key proteases for the degradationof toxic proteins, accumulate inmotile and reversiblegranuleswhich protect cells against stress and conferfitness during aging. They also found that ubiquitinis required for the formation of these proteasomegranules. How and why protein droplets such asproteasomegranulesare formed isoneof thehottestquestionsincellbiology.

Rubinstein lab uses cryo-EM to unveil new details about ATP generation in mitochondria (Science 2017358(6365):936-940)In the latest of a series of beautiful papers on thestructure of the mitochondrial ATP synthase, theRubinsteinlabprovidenewstructuralinformationonthecomplex,whichrevealshowprotonstravelthroughthismacromolecularassembly,howthiscomplexdimerizes,and how the dimers bend the inner mitochondrialmembrane to produce cristae,which are a feature ofmostinnermitochondrialmembranes.

Maxwell and Davidson labs help identify a new inhibitor of Cas9 (Cell2017170(6):1224-1233)In collaboration with the Doudna, Sontheimer andKranzusch Labs, the Maxwell and Davidson groupsdiscovered and characterized two different inhibitorsof Cas9 which prevent CRISPR-Cas9 mediated DNAcleavage. These proteins, which are produced bybacteriophagetopreventtheircleavageafterinfection,mayonedaybeusedtomodulatetheactivityofCRISPR-Cas9indiversegene-editingtechnologies.

The Houry lab maps the molecular chaperone network (CellReports201720(11):2735–2748)The Houry lab spearheaded an internationalcollaboration to provide a comprehensive view ofmolecular chaperone function in the cell throughthe use of a systematic global integrative networkapproach based on physical (protein-protein) andgenetic (gene-gene or epistatic) interaction mapping.Manychaperoneswerefoundtointeractwithproteinsthatformfociorcondensatesunderstressconditions,and this work provides novel insight into how theseintracellularaggregatesform.

Ernst Lab use DEER spectroscopy to determine how GPCRs use phosphorylation codes to recruit arrestin. (Cell2017170(3):457-469)G protein-coupled receptors (GPCRs) mediate diversesignalling in part through interaction with arrestins,whose binding promotes receptor internalization andsignalling through G protein-independent pathways.Featured on the cover of Cell, work from the Ernstlab inan international collaborationwithgroups fromthe U.S., Germany and China, helps to elucidate howGPCRsrecruittheirdownstreamtargetarrestinthroughphosphorylation. In particular, the Ernst lab useddouble electron-electron resonance (DEER), a formofpulsedelectronparamagneticresonancespectroscopytovalidatesomeaspectsofthecrystalstructureofthephosphorylated G-protein-coupled receptor (GPCR)rhodopsinincomplexwitharrestin.

Bear Lab shows that a new cystic fibrosis treatment improves function from a rare CFTR mutation in patient tissue(EMBOMolMed.20179(9):1224-1243)The laboratory of Christine Bear, together with thegroupofRégisPomèsandcollaboratorsatTheHospitalforSickChildrenandProteostasisTherapeutics,usedin silico,invitroandexvivotechniquestocomprehensively


understand the consequences of a rare cystic fibrosis(CF)disease-causingmutationintheCFTRgene:c.3700A>G(ΔI1234_R1239),andsubsequentlydevelopanovelmechanism-basedtherapeuticstrategy.

Howell lab deduces the mechanism of type IV pilus motors(NatureCommunications20178:14816)The type IV pilus is a long and sturdy grappling hookthat bacteria use to attach to a surface and thenpullthemselves closer to it. The molecular mechanismof themotors involved in throwingout andpulling inthese grappling hooks was deduced by the Howelllab, in conjunctionwith theBurrows labatMcMasterUniversity. They solved the structure of the motorATPasePilBinthepresenceofnon-saturatingamountsofeitheranATPanalogueorADP,representing“before”and “after” states of hydrolysis. This allowed for thedeductionofthemovementsmadeduringthehydrolysiscycle. They also extended this ATPase mechanism tothepreviouslysolvedstructureofasecondATPase,PilT,whichisresponsiblefortheoppositefunction:pulling-in the grappling hook by disassembling the pilus intopilinsubunits.

New genetic disease discovered by the Muise and Kahr labs(NatureCommunications20178:14816)Members of the Kahr andMuise labs discovered thatmutations in ARPC1B, a spliced isoform producedfrom theARPC1 gene, causemicrothrombocytopenia,eosinophiliaandinflammatorydisease.Theproductofthis gene forms part of theArp2/3 complex,which isrequiredforthepolymerizationofactinfibres.Thisworkcouldpavethewayfornoveltherapeutictreatmentsforthesepatients.

Ernst lab discovers new way to crystallize membrane proteins (Structure201725(2)384-392)The laboratory of Dr. Oliver Ernst has used X-raycrystallography to determine the structure of amembrane protein imbedded in a polymer-boundedlipid nanodisc. The newmethod expands the toolboxfor membrane-protein crystallography and promisesmorestructuresofproteins that so farhavenotbeenamenable to treatmentwith conventional detergents.TheirpublicationwasfeaturedonthecoverofStructure.

The roles of protein dynamics and water networks in catalysis visualized by the Pai, Prosser and Pomès labs (Science2017355(6322):eaag2355)

The laboratories of Emil Pai, Scott Prosser, RégisPomès and collaborators in the U.S. and Japan, useda combination of X-ray crystallography, NMR andcomputational techniques to delineate how inter-subunitinteractionsinthedimericenzymefluoroacetatedehalogenase contribute to enzymatic catalysis. Thisenzymeisoneofonlyahandfulofproteincatalyststhatcanbreakthestrongestbondinorganicchemistry,theonebetweencarbonandfluorineatoms,intheprocesstransforming the highly toxic pesticide fluoroacetateinto glycolate, a benignmolecule. Thiswork providesinsightsintohowsubstratesmodulatethestructureanddynamicsofanenzymetofacilitatecatalysis.

Stagljar lab map interactions between receptor tyrosine kinases and protein tyrosine phosphatases (MolCell.201765(2):347-360)Featuredon the coverofMolecularCell, research ledby Dr. Igor Stagljar usedmammalianmembrane two-hybrid(MaMTH)tomapinteractionsbetweenreceptortyrosine kinases and protein tyrosine phosphatasesin human cells. Thiswork provides a broad and deepviewof receptor tyrosinekinasesignalling,potentiallyleadingtonewandimprovedcancertherapies.

Faculty appointments:The Department was pleased to welcome three newfacultymembersin2017:

Dr. Hyun Kate Lee joinedthe Department with aprimary appointment asAssistant Professor. Katetrained in the lab of TonyHyman,whohaspioneeredour understanding ofbiomolecular phaseseparation, which enablesmolecules toself-assembleinto distinct organelleswithout membranes.Her work demonstratedthat disordered domains

(protein regionswithoutdefined secondary structure)function as a platform for phase separation. Because30%of the proteome is predicted to have disorderedregions, her finding is likely to have wide-spreadimplications in cellular organization and in disease.Moreover, she demonstrated that membraneless

Dr.HyunKateLee


organellescanconvertfromhavingliquid-likematerialproperties to form solid protein aggregates, and thatthisliquid-to-solidtransitionisacceleratedbymutationsondisorderedregions.Becauseproteinaggregationisakeymoleculardefectinneurodegeneration,herfindinghas implications for elucidating how these cytotoxicstructures arise in disease. Beyond the formation ofpathological protein aggregates, deregulating thematerial properties of membraneless organelleslikely influences their function and contributes tonumerous cellular defects. Her new lab will identifycellular mechanisms that regulate the ‘liquidity’ ofmembraneless organelles and how deregulating thisessential cellular process leads to degeneration ofneurons.

Dr. Joshua Currie also joined the Department asAssistantProfessor,withaprimaryappointmenttotheDepartmentofCellandSystemsBiology.Joshreceivedhis Ph.D. at the University of North Carolina, ChapelHill,withSteveRogers,studyingtheroleofmicrotubuleplus end proteins in microtubule dynamics and cellmigration. As a post-doctoral fellow, he worked inthe lab of Elly Tanaka at the Center for RegenerativeTherapiesinDresden,wherehewasanAlexandervonHumboldtandEMBOFellow.Hisnewlabwillutilize in

vivoimagingandmolecularcell biology of the highlyregenerative axolotl tounderstand principlesof tissue regeneration.Ultimately, thiswork in anorganism that is capableof amazing feats ofregenerationwillgivenovelinsightsintoincreasingtheregenerative potential oftissuesinhumans.

Dr.JoshuaCurrie

Dr. Nana Lee was hired by the Department as anAssistant Professor, teaching stream. Dr. Lee holdsa Ph.D. in Biochemistry from U of Toronto, a visitingscholar experience from M.I.T., and a post-doctoralfellowshipfromtheUniversityofMichigan.Shebringsheryearsofexperienceandexpertisefromthebiotechindustry (Ellipsis Biotherapeutics, DNA Software) intothe classroom with her internationally recognizedgraduate-level professional development curriculum-

embeddedcourseintheDepartmentsofBiochemistryandImmunologyattheUniversityofToronto.Shehasspoken toover 1,000 students, post-docs, faculty andcurriculum administrators in empowering trainees

in optimizing researchproductivity andp ro fe s s i ona l /ca ree rdevelopment. Dr. Lee’swork in professionaldevelopment has beenfeatured in Science Careers, the Council ofGraduate Schools/NSF,and the ConferenceBoardofCanada.

Dr. Nana Lee

Retirements (contributed by Jean-Philippe Julien andAngusMcQuibban):

EmilPaiwillberetiringfromtheDepartmentofBiochemistryinthe summer of 2018 after anillustriousscientificcareer.EmilobtainedhisPh.D.inChemistryfromRupertoCarolaUniversity,Heidelberg, Germany in 1978.After post-doctoral studies inthe Department of BiophysicsattheMaxPlanckInstituteforMedical Research, he becameGroup Leader at the same

institute,where he headed a research group for overtenyears.There,heremarkablydeterminedthethree-dimensional fold of the first oncoprotein, H-ras p21(Nature,1989;Nature,1990;Cell,1990),andsolvedthecrystal structure of themuscle protein actin (Nature,1990).

Emil was recruited to the Faculty of Medicine at theUniversityofTorontoasanNSERC IndustrialResearchChairinProteinCrystallography,wherehebecameFullProfessorinBiochemistry(1991),inMolecularGenetics(1991)andsubsequentlyinMedicalBiophysics(1996).Duringhis career, Emil heldaTier1CanadaResearchChairinStructuralBiology,wasHeadoftheDivisionofMolecular & Structural Biology at the Ontario CancerInstitute, anda Senior Scientist at theOntarioCancerInstitute/Princess Margaret Cancer Centre (University

Dr.EmilePai


Health Network). Emil contributed over 200 researchpublications during his career. Recently, he describeda breakthrough in the role of dimer asymmetry inenzyme catalysis (Science, 2017). His impact into thestructural determinants of protein function has beenbroad, including in the fields of molecular transport,antibodyrecognition,prionproteins,andflavoproteins.He has been an outstanding mentor to dozens oftrainees,generouswithhistimeservingonnumerouscommittees, andhas inspiredmany in his teaching attheuniversity.

Ascientific symposium inhishonourandcelebratinghis career “Why Structure Matters” will be held attheUniversityofTorontoonJuly19th2018.Welookforwardtothisevent,whichwillre-unitemanyofhiscolleagues and friends. Emil, many thanks for yourinspiringwork throughout your career.Wewish youwellonyourretirement.

Peter Lewis will be retiring from our Department insummer 2018 after 44 years as a facultymember.HejoinedourDepartmentasanAssistantProfessorin1974,followingpost-doctoral studieswithMortonBradburyin theUK.Over the years Peter has taught legions ofundergraduates, graduate students and post-doctoralfellows in the intricacies of protein and chromatinstructure,whiledelvingintotopicssuchasAlzheimer’sDiseaseandaging.Since1991,Peterhasheldanumberof facilitative roles includingDepartmentChair (1991-2001), CSBMCB President (1999), ViceDean Researchand InternationalRelations in theFacultyofMedicine(2002-2010) and Associate VP Research - GlobalResearchPartnerships in SimcoeHall (2010-2016).He

has been involvedin the formation ofmany UofT entitiesincluding theDonnellyCCBR and theStructural GenomicsConsortium. Centrally,he was involved inrestructuring the UofTTech Transfer Office(now IPO) and thecreation of SOSCIP,CCRM and CCAB.Since returning to theDepartmentin2016as

a“plainprofessor”,asPeter’swifeLindaputs it,Peterhas teamed up with Professor Angus McQuibban tocreateastart-upcalledRosettaTherapeuticsaimedatdrug discovery for neurodegenerative diseases usingexperimentalanddeeplearningapproaches.Peterlooksforwardtotransitioningintoretirementbyparticipatinginthestart-up,spendingmoretimeonhisnewhobbyof power boating, and of course relaxing with Linda,andsons,ColinandPatrickandtheirchildrenAryaandKalise.Timetosmelltheroses!!Petercanbereachedathttp://biochemistry.utoronto.ca/person/peter-n-lewis/

Departmental events:Department retreatThesecondannualBiochemistryDepartmentalRetreatwasheldat theKempenfeltCentreonAugust30-31,2017.TheretreatnotonlyallowedtheDepartmenttocelebrate our newest scientific discoveries, but alsoallowed everyone to see old friends and meet newcolleagues.Italsoallowedincominggraduaterotationstudents to sample all of the exciting science that ishappening throughout the Department. This year,the retreat focussed on grad students and includedscientificpresentationsfrom21trainees. Inaddition,weheardProfessorHaleyWyatttalkaboutherexcitingworkinthefieldofDNArepair.Otherhighlightswerethe poster session where grad students, post-docsandundergrads got to showoff their latest findings,thephotoscavengerhuntwhichtestedthe ingenuityand creativity of the various participating teams,faculty reading Mean Tweets from their students,and of course the evening bonfire,which included aspectacularsunset.

Golf DayIt was a dreary day on June 13th, but it would takemore than a few showers to dampen the spirits ofthe 24 intrepid biochemists who headed out to theFlemingdon Park 9-hole Golf Course in midtown

Participants in the second annual Biochemistry DepartmentRetreat

Dr. Peter Lewis


TorontofortheannualBiochemistryDepartmentGolfDay.Eachteamhaditsshareofbeginnersandringersplayinga“bestball”formatthatallowedeveryonetocontributetotheirteam.Despitespendingmorethanalittletimeunderumbrellas,thecompetitionremainedfiercewiththeERADicalssqueakingoutabirdieonthe9thholetosnatchthewinfromtheRightLeftiesandtheDeadRingerswhowereonlyastrokebehind!

TheannualBiochemistryDepartmentGolfDayatFlemingdon Park

Graduate student news:RotationsThis past fall the Department instituted a rotationsystem for its incoming graduate students. Thesystemworksbystudentsengaginginthreefive-weekrotations during their first semester of study, fromSeptembertoDecember.Thena lab ischosenwithamutual agreement between supervisor and student.As they rotate, all of the students areenrolled in anEffectiveScienceCommunicationclasscoordinatedbyAlexPalazzo,AlexEnsmingerandNanaLee.Briefly,thestudents learnhowtogiveaneffectivepresentation,how to write a scientific report, how to provideeffective feedback, and how to engage and networkamongsttheirpeers.

The overwhelmingly majority of both faculty andstudentsagreed that the first implementationof therotation system was a success. Interestingly, almosttwothirdsofallrotationstudentsendedupjoiningalab thatwasdifferent from theiroriginalpreference,and this was largely due to students making muchmoreinformedchoicesafterhavingrotatedindifferentenvironments.

University of TorontoDepartment of Cell and Systems BiologyCorrespondent:TonyHarris

We are a major contributor to research and teachingattheUniversityofToronto.GroupsintheDepartmentcombine high-throughput, cell imaging, physiologicalandbioinformaticsmethods tounderstandcellularandphysiological processes in both model (Arabidopsis,C. elegans, Drosophila, mouse, Xenopus, zebrafish,axolotl and cell culture) and non-model organisms.The Department’s major strengths include its groupsstudying plant molecular biology, its labs focussed onanimal cell biology and tissue morphogenesis, and itsgroupsstudyingneurophysiology.TheDepartmentisalsohometotheCentrefortheAnalysisofGenomeEvolutionand Function, a CFI-funded centre for genomics andproteomicsresearch,inadditiontoastate-of-the-artCFI-fundedmicroscopycentre.

Twonewfacultymembersstarted thisyear.Dr. Arneet Saltzman studies chromatin regulation underpinningC elegans development. Dr. Joshua Currie studiesmolecular and cellular mechanisms of axolotl limbregeneration.

Jennifer MitchellwaspromotedtoAssociateProfessor.Chris Garside was promoted to Associate Professor,TeachingStream.Belinda Chang, Eiji Nambara, Melanie Woodin,andKeiko YoshiokawereallpromotedtoFullProfessor.

Prof Melanie Woodin was appointed Associate Dean,Undergraduate Issues and Academic Planning. Prof.Ashley Bruce was appointed Director of the HumanBiology Program. Prof. Ulrich Tepass is the newCanadaResearchChair (Tier I) inEpithelialPolarityandDevelopment. Prof. John Calarco has been awarded aCanadaResearchChair(Tier2)inNeuronalRNABiology.

Notablepublicationsincluded:

Evolution of nonspectral rhodopsin function at highaltitudes.Castiglione GM, Hauser FE, Liao BS, Lujan NK, VanNynatten A, Morrow JM, Schott RK, Bhattacharyya N,DunganSZ,Chang BSW.ProcNatlAcadSciUSA2017Jul11;114(28):7385-7390.


Anactomyosin-Arf-GEFnegativefeedbackloopfortissueelongationunderstress.WestJJ,Zulueta-CoarasaT,MaierJA,LeeDM,Bruce AEE, Fernandez-Gonzalez R, Harris TJC.CurrBiol2017Aug7;27(15):2260-2270

ExpandedtypeIIIeffectorrecognitionbytheZAR1NLRproteinusingZED1-relatedkinases.SetoD,KoulenaN,LoT,MennaA,Guttman DS, Desveaux D.NatPlants2017Mar13;3:17027

Specification and spatial arrangement of cells in thegermlinestemcellnicheoftheDrosophilaovarydependontheMaftranscriptionfactorTrafficjam.PanchalT,ChenX,AlchitsE,OhY,PoonJ,KouptsovaJ,LaskiFA,Godt D.PLoSGenet2017May19;13(5):e1006790

Selectionmaintainssignalingfunctionofahighlydivergedintrinsicallydisorderedregion.ZarinT,TsaiCN,NguyenBaAN,Moses AM.ProcNatlAcadSciUSA2017Feb21;114(8):E1450-E1459

ePlant:Visualizingandexploringmultiple levelsofdataforhypothesisgenerationinplantbiology.WaeseJ,FanJ,PashaA,YuH,FucileG,ShiR,CummingM,KelleyLA,SternbergMJ,KrishnakumarV,FerlantiE,MillerJ,TownC,StuerzlingerW,Provart NJ.PlantCell2017Aug;29(8):1806-1821

Myosin II promotes the anisotropic loss of the apicaldomainduringDrosophilaneuroblastsingression.Simões S, Oh Y, Wang MFZ, Fernandez-Gonzalez R, Tepass U.JCellBiol2017May1;216(5):1387-1404

Visual experience facilitates BDNF-dependent adaptiverecruitmentofnewneuronsinthepostembryonicoptictectum.HallZJ,Tropepe V.JNeurosci2018Feb21;38(8):2000-2014

Ingression-type cellmigrationdrives vegetal endoderminternalisationintheXenopusgastrula.WenJW,Winklbauer R.Elife2017Aug10;6

RestoringGABAergicinhibitionrescuesmemorydeficitsinaHuntington’sdiseasemousemodel.Dargaei Z, Bang JY, Mahadevan V, Khademullah CS,BedardS,ParfittGM,KimJC,Woodin MA.ProcNatlAcadSciUSA2018Feb13;115(7):E1618-E1626.

University of TorontoDepartment of Molecular GeneticsCorrespondent:BarbaraFunnell

MolecularGeneticshadabanneryear in2017fornewrecruits,bothstudentsandfaculty,andneweducationalinitiatives.Werecruitedover75newgraduatestudentsand7newfacultymemberstothecoregroup,withourpartnernodesatSickKidsandtheDonnellyCentre,andtosupportthenewMastersdegreeinMedicalGenomicsthatwillbeginintheFallof2018.

Welcome to new faculty:Dr. Thomas HurdjoinedtheDepartment as anAssistantProfessor in January 2018,intheMoGencoreatMaRS.His research program isfocussed on determininghow mitochondrial DNAis inherited through thefemale germline, and howmitochondriainfluencestemcell fate and differentiationin vivo, with a long-terminterest in applying this

knowledgetodevelopbetterprotocolsforreprogramminganddifferentiatinghumanstemcellsinvitro.

Dr. Aaron ReinkejoinedtheDepartment as an AssistantProfessor in September2017,intheMoGencoreatMaRS.Hisresearchprogramisfocussedonauniquemodelsystem of microsporidialparasites that infectworms,specifically studying co-evolution of Caenorhabditis nematode hosts andNematocida pathogens.His research encompasses

Dr.ThomasHurd

Dr. Aaron Reinke


interdisciplinary approaches with biochemistry, genetics,systemsbiology,andtechnologydevelopment.

Dr. Ryan YuenisaScientistin Genetics and GenomeBiology at the Hospitalfor Sick Children, andjoined the Departmentas an Assistant Professorin 2017. Dr. Yuen studieshowgeneticandepigeneticvariations contribute tohumanhealth,withafocuson neurodevelopmentalandneurologicaldisorders.

Dr. Hannes RӧstjoinedtheDepartmentasanAssistantProfessor in 2017, in theDonnellyCentreforCellular& Biomolecular Research.His research interests aretounderstandbiologyonapersonalized level and hislab uses next-generationmass spectrometry toanalyze proteomic andmetabolomic data in high-throughput.

New Professional Master’s Program in Medical Genomics:MolecularGeneticsislaunchinganewM.H.Sc.inMedicalGenomics,whichwillbe thefirstof itskind inCanada.The programwill target both clinically and laboratory-focussedstudents,andwillprovideauniquetrainingandlearningenvironmenttoteachpracticalandtheoreticalaspectsofmoderngeneticsandgenomicswithastrongfocusonclinicalapplication.Thistwo-yearcourse-basedgraduateprogramwill consist of a core setof courses,comprising lectures, discussions, projects, and casestudies, and will culminate in a hands-on CapstonePracticum. Students graduating from the program willobtain professional and practical skills that will helpsituate them in aworld inwhich genetic and genomicdataareroutinelycollectedandanalyzedacrossawiderangeofpatientpopulationsandmedicalindications.Weare currently recruiting our first cohort of students tostartinSeptember2018.

In2017,werecruitedthree facultymembersasAssistantProfessors,TeachingStream,todesignandimplementtheM.H.Scprogram.Welcometo:Dr. Erin Styles istheDirectorofthenewMastersofHealthSciencesprograminMedicalGenomics.ShecompletedherPh.D.withBrendaAndrewsinMolecularGeneticsattheUofToronto.Dr. Martina SteinercompletedherPh.D.atETHZurich,andholdsaMaster’sdegreeinSecondaryandHigherEducation.Dr. Johanna Carroll receivedherPh.D.attheUniversityofCalifornia Berkeley, and did post-doctoral training at theDanaFarberCancerInstituteandHarvardMedicalSchool.

Faculty highlights and awardsDr. Janet RossanthasbeenrecognizedbyUNESCOandthe

L’OréalFoundationasoneoffive outstanding womenscientists from around theworld, with a 2018 L’Oréal-UNESCO For Women inScience Award. Dr. Rossanthas also been honouredwitha2017honoraryDoctorof Science degree fromCambridge University. Dr.Rossant is being honouredfor her contribution to theunderstandingofhowtissues

andorgansareformedinthedevelopingembryo.

Dr. John Dickisthe2017recipientof the inauguralCIHRGoldLeafPrizeforDiscovery,andhasalsobeen awarded the 2017 KeioMedical Science Prize by KeioUniversity in Japan. Dr. Dick isrecognized for his contributionsto the understanding of cancerstemcellsandcancer.

Dr.RyanYuen

Dr.HannesRӧst

Dr.ErinStyles Dr.MartinaSteinerDr.JohannaCarroll

Dr.JanetRossant

Dr.JohnDick


Dr.JohnDick

Dr. Lewis Kay has beenrecognized with a2017 Canada Gairdner International Award“For the development ofmodernNMRspectroscopyforstudiesofbiomolecularstructure dynamicsand function, includingapplications to molecularmachinesandrareproteinconformations.”

Dr.LewisKay

Dr. Brenda Andrews hasbeenappointedtotherankofUniversityProfessor,thehighest academic rank atthe University of Toronto.Dr. Andrews is recognizedfor extraordinary scholarlyachievement andleadershipattheUniversity.In addition, Dr. Andrewshas been appointed tothe governing council ofthe Canadian Institutes ofHealthResearch(CIHR).

Dr. Stephen Scherer hasbeen honoured with a2017 Honorary Doctorof Science from theUniversity of Waterloo,for his “ground breakingcontributions to theunderstanding of geneticvariation, especially as itrelates to human healthanddisease”.

Dr. Stephen Scherer

Canada Research Chairs:Eight faculty members from Molecular Genetics havebeennamedCanadaResearchChairsin2017:Dr. John Dick - Tier1CanadaResearchChairinStemCellBiology

Dr. C.C. Hui - Tier 1 Canada Research Chair in MouseDevelopmentandDiseaseModellingDr. Lucy Osborne - Tier 1 Canada Research Chair inGeneticsofNeurodevelopmentalDisordersDr. Frank Sicheri - Tier 1 Canada Research Chair inStructuralPrinciplesofSignalTransductionDr. Julie Claycomb - Tier 2 Canada Research Chair inSmall RNA BiologyDr. Ran Kafri - Tier2CanadaResearchChairinQuantitativeCell BiologyDr. Jason Moffat - Tier 2 Canada Research Chair inFunctionalGeneticsDr. Jeehye Park - Tier 2 Canada Research Chair inMolecularGeneticsandNeurodegenerativeDiseases

Trainee awards:The Barbara Vivash Award for best Ph.D. Thesis: TheVivashaward is givenannually toagraduating studentwiththebestPh.D.thesis,andwehavetworecipientstoreportsincethelastCSMBnewsletter.Dr. Ryan Gaudetreceivedthe2016BarbaraVivashAwardfor his thesis, entitled TIFA-Mediated Innate ImmuneRecognitionoftheBacterialMetaboliteHBPanditsRoleinHostDefense”.RyancompletedhisPh.D.withDr.ScottGray-Owenexamininghowcellsrespondtoandpromoteimmuneresponsestobacterial infection.Ryanisnowapost-doctoralfellowatYaleUniversity.Dr. Serge Gueroussov was awarded the 2017 BarbaraVivash Award for his thesis, entitled “FunctionalConsequences of Mammalian-Specific AlternativeSplicing Events in RNA Binding Proteins”. Serge’sPh.D. studies, with Ben Blencowe, examined roles foralternative splicing in the brain. Serge is now a post-doctoralfellowattheBroadInstituteofMITandHarvard.

Dr.RyanGaudet Dr.SergeGueroussov

Dr. Brenda Andrews


MolecularGeneticsalsohasseveralcompetitiveawardsandfellowships,givenannuallytoourgraduatestudents.Congratulationstoallrecipients!!Theyare:Harley Mount (Ensmingerlab):L.W.MacphersonAwardKaitlin Laverty(Hughes/Morrislabs):RomanPakulaAwardDustin Ammendolia (Brumell Lab): Norman BethuneAwardElissa Currie(Gray-Owenlab):EricHaniFellowshipBrendan Innes(Baderlab):DavidStephenCantGraduateScholarshipinStemCellResearch

Departmental and community events:3rd Annual MoGen Career Development SymposiumEmpowering trainees and engaging alumni are ourprimary goals for the Career Development symposiaseries started in 2015. The 3rd AnnualMoGen CareerDevelopmentSymposiumwasheldon June9,2017,attheChestnutConferenceCentre,organizedbyDrs.LeahCowenandBarbaraFunnell.Themissionofoursymposiais to providementorship for our trainees in themanycareer options available to them by highlighting thepaths followedby themanyextraordinaryalumni fromMolecularGenetics.Theafternoonincludedround-tablediscussions between alumni and trainees, networkingsessions, and a panel discussion by six distinguishedalumni: Dr. Jacques Archambault (Professor, McGillUniversity), Dr. John Calarco (Assistant Professor,UniversityofToronto),Dr.FrédéricSweeney(VPBusinessDevelopment&StrategicAlliances,bioMérieuxSA),Dr.Elizabeth Higgins (Analytical Development & QualityControl, GE Healthcare Life Sciences), Dr. MelanieSzweras(Partner,Bereskin&ParrLLP),andDr. JenniferSemotok (SeniorGeneticCounsellor,GeneDX).Wearealreadyplanningour4thsymposium,whichwillbeheldonJune4,2018attheChestnut.Pleasejoinus!

MoGen Retreat 2017:We gathered for our 2017Molecular Genetics Retreatat Geneva Park YMCA, on September 20th-22nd. TheretreatwasorganizedbyDr.JimRini,Dr.JulieLefebvre,andDr.LeahCowen,withtheassistanceofEricChapman,Samantha Esteves, Lauren Tracey, and theirGSA team.Attendancewasoutstandingwithalmost300participants,including faculty and trainees. The retreat showcasesresearchfromacrosstheentiredepartment.Itconsistedofseveralshortfacultytalks,especiallyhighlightingournewest faculty members, and a poster session with arecord 137 presentations. The event always includesaneveningofentertainmentorganizedbythegraduate

students,followedbycelebrationsthatgointothenightatthefirepits,andwithmusicanddancingintheBarn.Thankstoallforasuccessfulretreat!

Participantsatthe2017MolecularGeneticsRetreat

Move to MaRS!:The move of a large number of MoGen core labs to theMaRSWestTowerfromtheMedicalSciencesBuildingiscomplete,andwearesettlingintoournewspace.Labsareonthe15thand16thfloors,andwesharethespacewithcolleagues fromthedepartmentsofBiochemistry,Lab Medicine & Pathobiology, and Medicine. The twofloorsaredifferentiatedapproximatelybytheme:MaRS15isGene-ProteinRegulation,andMaRS16isMolecularMicrobiology&InfectiousDisease.

March for Science:ThousandsofsciencefanstooktothestreetsofTorontoonApril22forthe“MarchforScienceToronto”rally,oneofover600suchmarchesacrosstheglobeinsupportofscientificresearch.Manystudents,post-docs,professorsand staff fromMoGen were evident. As a nationwideevent,theMarchforSciencewasnotonlyacelebrationofscientificachievements,butwasalsoademonstrationofalltheimportantcontributionsthatsciencehasmadetosociety.

The“MarchforScienceToronto”rally


.University of Toronto MississaugaDepartment of Chemical and Physical SciencesCorrespondent:VoulaKanelis

New faculty member:Sarah Rauscher joined thedepartment in August 2017.Sarah completed her Ph.D. inBiochemistry at theUniversityof Toronto and SickKids in thelaboratory of Régis Pomès.She then moved to the MaxPlanckInstituteforBiophysicalChemistry in Göttingen tocarry out post-doctoral workin the department of HelmutGrubmüller.Herlabiscurrently

developingaccurateandefficientsimulationmethodstostudy disordered proteins and protein dynamics in all-atom detail. https://www.utm.utoronto.ca/cps/faculty-staff/rauscher-sarah

ProfessorRauscherjoinsotherUTMcolleaguesontheorganizing committee for the Biophysical Society ofCanadameeting,whichwillbeheldatUTMinlateMay2019.

Faculty news:Andrew Beharry’s research is at the interface ofbiochemistryandmedicinalchemistry.HislabhasgrownsinceheobtainedhisownlabspaceinMay2017,andnowcomprises14personnel.Thispastyearhisgrouphas synthesized a series of smallmolecule probes forfluorescence-guidedphotodynamictherapy,whichtheyarecurrentlytestingincancercells.Andrew’smugwasfeaturedonthecoverofACSBiochemistryinaspecialissue titled, “The Future of Biochemistry” and hewasinvitedtowriteareviewonthefieldofsmallmoleculefluorescent sensors for ACS Chemical Biology. He issuper-eager to publish his first set of research-basedpapersthisyear!

Professor Patrick Gunning and his group continue tomakestridesinthegenerationofdrugsagainstcancer.For more information on the Gunning group, pleasesee:http://www.gunninggroup.ca/home.

Professor David McMillen received his third GrandChallenges Canada Stars in Global Health grant,“Locally-produced algae for protein, iron, and vitaminsupplementationinchildren”.Theprojectseekstodeveloppractical methods of deploying the cyanobacteriumArthrospira platensis (commonly known as Spirulina)as a source of nutrition in low-resource areas in thePhilippines.Spirulina is aphotosyntheticorganism thatproduces all essential amino acids, has a high proteinand vitamin content by mass, and delivers significantquantities of bioavailable iron, which is particularlysignificantinthePhilippineswhereanaemiaiscommoninchildren.Prof.McMillenspentaportionofhissabbaticalyear in the Philippines, working with local partners toset up Spirulina growth facilities using locally-availableresources and conduct preliminary investigations ofdistributionmechanisms,suchasincorporatingthecellsinto noodles. Though the McMillen lab mainly workson more “high tech” projects involving engineeredmicrobes intherapeuticorsensingcontexts,thisworkreflectsProf.McMillen’schangingfocuswhenitcomes

Dr. Sarah Rauscher

CoverforthespecialissueofBiochemistry;ProfessorAndrewBeharry’smugisinthetoprow,5thfromtheleft.


toproblem-solvinginthedevelopingworld:“Ifthere’sa natural organism thatdoeswhatweneed, let’s notengineer it just because we can. If it later turns outthatweneedtotweakitsomehow,wecandothat,asrequired.Whateverworks!”

PhotosofSpirulinagrowinginjugs.NotethatProf.McMillenacknowledgesthatthechickeninthephotoontheleftisnotamemberoftheteamandhasyettosignaphotoreleaseform.

ImageofSpirulinaunderthemicroscope.Spirulinaassociatesasmulticellularstructuresthatformlongspirals,makingthemeasytoharvestfromsolutionwithanylonmesh.

Voula Kanelis and her group study ABC proteins andHNHendonucleases. Theirwork on the SURproteins,which are ABC proteins that form the regulatorysubunitsinKATPchannels,waspresented(byV.Kanelis)at the University of Alberta as part of the WalterMacKenzieVisitingSpeakerFund,andattheCSMB61st

Annual Conference on Membrane Proteins in HealthandDisease.HighlightsfromthegroupalsoincludethegraduationofMiriam ParkwithanM.Sc.degreeandDr. Claudia Alvarezwith a Ph.D. degree.Sasha Weiditch, aPh.D.candidate,receivedtheUTMGraduateStudentLeadershipAwardandcontinuesheroutreachactivitiespromoting science and scientists. Notably, Sasha wasselectedtospeakaboutheroutreachactivitiesonsocialmediaattheUofTTEDxDeconstructconference.

FemalestructuralbiologistsfromtheKanelis,Prosser,andABEgroupsatUTMontheInternationalDayofWomenandGirlsinScience

Theyear2017sawthe labof Scott ProsseradvancingtheirstudiesinenzymesandGPCRs,andpickingupnewstudents(JeromeGouldandChrisDiPietrantonio)whoaretakingthe leadonallostericnetworks inenzymes,and in the design of new chemical probes for NMR.After receiving the 2017 Jeremy Knowles Award fromthe Royal Society for Advances in Chemistry at theInterfacewithBiology,ScotttravelledtotheU.K.togivelectures on GPCR and enzyme allostericmechanisms.Unfortunately, Mother Nature had other plans and afreak snow storm kept him from ever making it pastCambridge and Oxford. The lab later received a JELFCFI award which they will make use of to refurbishtheirproteinexpressioncapacityforreceptorresearch. Kate Huang (Prosser Lab) receivednews that shewill


bereceivinganNSERCAlexanderGrahamBellCanadaGraduate Doctoral Scholarship. Her work has so farfocused on allosteric players in the cell that regulateGPCRsignaltransduction.

Jumi Shin’sgroupcontinuestomakestridesindesigningDNA binding proteins. The Shin group’s designedminimalistproteinME47isananti-proliferativeagainsta triple negative breast cancer tumor xenograft in amouse model. This was published in Oncogene, doi:10.1038/onc.2017.275.ME47canbedeliveredtobreastcancercellnucleiandbindstothesameDNAtargetsasdoesoncoproteinMyc/Max,atranscriptionalactivatorinvolved in >50% of breast cancers. Thus ME47 is acompetitive inhibitor.TheShingroupalsopublishedareviewarticle,“Peptidetherapeuticsthatdirectlytargettranscription factors,” for an issue of Peptide SciencefocusingonCanadianlabs(doi:10.1002/pep2.24048).

Outreach activities:Inkeepingwiththethemeofoutreach,Voula Kanelis, co-director Professor Steven Chatfield (UTM Biology)and technicianKristina Han successfully launched theAmgenBiotechExperienceCanadasite,whichprovidesteachers with training, reagents, and equipment toconductbiotechnologyexperimentsintheirclassrooms.In the first year, the program will have trained 20teachersandprovidedgreaterthan300studentswithhands-onbiotechlabexperience.


CSMB-Sponsored Events

McGill UniversityAnnual McGill Biomedical Graduate Conference (AMBGC)Correspondent:WilliamLiu

For the last 16 consecutive years, the ExperimentalMedicine Graduate Student Society (EMGSS) of McGillUniversity has hosted the Annual McGill BiomedicalGraduate Conference (AMBGC). The EMGSS is a non-profit,studentrun,academicorganizationthatrepresentsgraduatestudentsandpost-doctoralfellowsregisteredintheDivisionofExperimentalMedicineatMcGillUniversity.

The AMBGC is a oneday symposium which allowsoutstanding graduate and undergraduate students theopportunity to present their research. Students fromuniversitiesacrossQuebecparticipate in the conferenceand participation is open to any student around theworld. Attendees are given an opportunity to interact,presenttheirwork,andlearnfromfellowmembersofthescientificcommunity.Post-doctoralfellowswithexpertiseinthevariousprogramslistedbelowvolunteerasjudgestoawardprizestoattendeesbasedonthemeritoftheirpresentations.Oneoutstandingabstractfromeachof

the categories below is also selected for an oralpresentation,which is judgedbyprincipal investigatorsat McGill, who also volunteer their time. The goal ofthis conference is to provide training opportunities forgraduatestudentsfromalllabs,regardlessofbudgetaryrestrictions. In this vein, the AMBGC does not chargea registration fee. We rely for the most part on thegenerosity of academic and corporate sponsors tofinanceourconference.

The17thAMBGC tookplaceonThursday,March23rd,2017 at the Omni Hotel, 1050 Rue Sherbrooke Ouest,Montreal. In recent years, the number of attendeeshas ranged from 150-200. Participants includedundergraduate and graduate students, post-doctoralfellows,universityfaculty,corporaterepresentatives,andcommunitymembers.

Graduate eventsTheCSMBprovidesfinancialsupporttograduatestudentsocietiesforavarietyofactivitiesrelatedtobiochemistry,molecularbiology,cellbiologyorgenetics.Examplesofsupportedactivitiesinclude(butarenotrestrictedto)thefollowing:

Scientific Symposium Days, withinvitedscientistsspeakingonsubjectsintheareasofbiochemistry,molecularbiology,cellbiologyorgenetics.Student Research Conferences,wherestudentsdisplaytheirresearchasposters,orgiveoralpresentations.Career Fairs or Career Workshops inareasrelatedtobiochemistry,molecularbiology,cellbiologyorgenetics.

The society will support up to six eventseachyear, toamaximum of $500perevent,onacompetitivebasis.StudentorganizationsseekingfinancialsupportunderthisprogramshouldcontactthesocietySecretarywithashortdescriptionoftheplannedevent,andtheamountoffundingrequested.TherequestshouldalsoincludeaRegularMemberoftheSocietyasaSponsor/Coordinator,workingwiththeStudentOrganization.Requestswillbeacceptedtwiceeachyear(upto3possibleawardsforeachcompetition),withdeadlinesofFebruary 15 and September 15.


Themesfortheconferenceincluded: •CardiovascularandRespiratorySystems •GeneticsandGeneExpression •Neuroscience •EndocrinologyandMetabolism •MicrobiologyandImmunology •Oncology •Epidemiology,BioethicsandMedicalGenetics •CellularandMolecularBiology

The keynote address this year was given by Dr. KeithMostovfromtheUniversityofCalifornia,SanFrancisco(UCSF). Dr.Mostov received his Ph.D. from RockefellerUniversityin1983,andhisM.D.fromCornellUniversityMedical College just a year later in 1984. Dr. Mostovhas made many extremely important contributions tothefieldof cellularbiology.Heuncoveredmanybroadandwidely accepted principles in polarizedmembranetrafficking. His lab went on to describe a detailed,multistep cellular andmolecularmechanism toexplainhowepithelialtubesformandelongate.Afterwards,theyworkedoutadetailedmolecularpathwaytoexplainhowthecellsinthesetubesorientanddeveloppolarity,andassemble the apical surface at the lumen. His keynoteaddressfocussedonthemostrecentproject inhis lab,studying the control of length of epithelial tubes inmammals; itwas attended by about 150 students andpost-doctoral fellowswho thoroughly enjoyed his veryinterestingandinteractivelecture.

TheaudienceatoneoftheAMBGCsessions

Participantsatthisyear’s17thAMBGC

Studentorganizersofthisyear’s17thAMBGC

McGill UniversityGoodman Cancer Research Centre Research DayCorrespondent:PaulaPintoCoelho

The GCRC is an internationally renowned institutioncommitted to conducting basic cancer research, andhas labs doing research in a wide range of topics inbiochemistry,molecularbiology,immunology,cellbiologyandgenetics.Biannually, theGoodmanCentre StudentSociety (GCSS) hosts the GCRC Research Day. GCSS isa non-profit student-run academic organization thatrepresents graduate students registered across severaldifferent departments (Biochemistry, ExperimentalMedicine, Physiology and Immunology among others)whoworkwithintheGoodmanCancerResearchCentre(GCRC)orinoneofitsaffiliatedlaboratories.

The GCRC Research Day is a one-day symposium thataimstocreateaplatformforinteractionandnetworkingacross allmembersof the centre.During theResearchDay, graduate students and post-doctoral fellows havetheopportunity toparticipateand compete ina seriesof events such asmini-TED talks, poster presentationsand short talks, which are judged by professors fromthe GCRC to award prizes based on themerit of theirpresentations.

The goal of the GCRC Research Day is to give theGoodman trainees the opportunity to make a


statementwiththeirwork,andtofosterinteractionandcollaborationacrossmembersofthecentre,promotingtheexchangeofnewideasandtechnologies,regardlessofbudgetaryrestrictions.Thus,theGCRCResearchDaydoesnotchargearegistrationfee,andinsteadreliesonthe generosity of academic and corporate sponsors tofinanceourconference.

The 3rd GCRC Research Day took place on October27th,2017attheRosalindandMorrisGoodmanCancerResearchCentre,1160AvenuedesPinsOuestMontreal.We had 100-150 attendees, and over 50 presenters,which included graduate students, post-doctoralfellows and research associates. In 2017, our student-invitedkeynotespeakerwasDr.RosaPuertollano,fromtheNational Institutes ofHealth,who is renowned forher work on molecular mechanisms of intracellulartrafficking and how this can contribute to humandiseases.Dr.Puertollanohaspublishedover50researcharticles, reviews, and book chapters and is a memberoftheeditorialboardofseveral journalssuchasTrafficand ISRNCell Biology.During the2017GCRCResearchDayshepresentedatalkentitled:Emergingnewrolesoflysosomes in health and disease.

Overall the organization of the GCRC research dayprovides an occasion for trainees working in varioussub-disciplines to come togetherandcontribute to theconcepts,knowledgeandunderstandingofeachother’swork,ultimately leading to theadvancementofcancerresearchforthebenefitofoursociety.

ParticipantsatoneofthesessionsattheGCRCResearchDay

Postersessionsatthe3rdGCRCResearchDay

Postersessionsatthe3rdGCRCResearchDay


University of Guelph, College of Biological SciencesGraduate Student Symposium 2017Correspondent: Dita Moravek

The College of Biological Sciences Graduate StudentSymposiumisanannualstudent-runeventthataimstoencourage scientific communicationbetween students,research fellows and professors within the threedepartments of the college, Molecular and CellularBiology, Integrative Biology, and Human Health andNutritionalSciences.

This year’s event took place on April 27 2017 in theSummerleeScienceComplexattheUniversityofGuelph,and welcomed approximately 220 attendees, withrepresentation from all our departments. More than100of theseattendeespresentedtheir researcheither

orallyorwithaposter,whichprovidedahugerangeofinterestingtopicstolearnabout.

Theevent also includes apresentation froma keynotespeakerabouttheirresearch.ThisyearfeaturedakeynoteaddressbyDr.WilliamMilsom,fromtheDepartmentofZoologyattheUniversityofBritishColumbia.Dr.Milsom’sresearch is directed at determining the physiologicalbasis of biodiversity in vertebrates, and his lab studiesthe respiratory, cardiovascular, thermoregulatory andmetabolic adaptations for life in environments withlow/highlevelsofoxygen,carbondioxide,temperature,food, and water. Dr. Milsom presented strategies thatvarious avian species use to adapt to different oxygenlevels, speakingto informationrelevantand interestingto all attendees, and giving an engaging and thought-provokingtalk.

Thisdaywasahugesuccess,thankstotheparticipants,and the organizing committee composed of graduatestudents and faculty; Sarah Bates, Shawn Beaudette,Alison Berezuk, Liz Johnston, Dennis Larson, GregoryMacNeill, Sahar Mehrpooyan, Dita Moravek, WillemPeppler, SarahSchorno,KatherineSuitor,GlenVanDerKraak,KarenWhite.

University of OttawaFaculty of Medicine 9th Annual Post-doctoral Research DayCorrespondent:UjvalAnilKumar

In collaboration with the Faculty of Medicine, theFacultyofMedicinePost-DoctoralAssociationorganisedits 9th Annual Post-doctoral Research Day on March16th,2017.Theeventwasahugesuccess,anddrewalargenumberofPDFs, researchassociates, faculty,andstudents from across the university. The day featuredthree oral presentations from post-docs on topicscoveringneuralstemcells,polycysticovariansyndromeandAlzheimer’sdisease,andwerejudgedbythefaculty.ThiswasfollowedbyakeynotepresentationfromDr.JimWoodgett(UniversityofToronto),andapostersession.Theeventshowcasedhighqualityresearchconductedattheinstitutioninavarietyoffields,andwasattendedbymorethan60people.

The poster session featured submissions from broadcategories, ranging from emerging technologies,Dr.WilliamMilsomgivinghiskeynotepresentation


neuroscience, biochemistry, microbiology andimmunologytohealthsciences.Theeventwasorganizedwiththesupportofanumberofsponsors,includingtheFacultyofMedicineitself,theOttawaHospitalResearchInstitute,andCanadianSocietyforMolecularBiosciences.Post-docs were awarded prizes for oral and posterpresentations.Wewould like to thank all participants,especiallythePDAexecutiveteamformakingthiseventahugesuccess,theFacultyofMedicine,OHRIandCSMBfor their generous support. We hope to see you nexttime!

Dr.JimWoodgettdeliveringakeynotepresentation

Post-docsattheResearchDayenjoyingacoffeebreak

Poster session

Poster session

Bulletin - Canadian Society for Molecular Biosciences · necessaryingredientsof great people,great...

Documents

Transcript of Bulletin - Canadian Society for Molecular Biosciences · necessaryingredientsof great people,great...