BIOM 2860: Molecular Mechanisms of Human Disease Contact … · 2019. 1. 23. · 1 BIOM 2860:...

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BIOM 2860: Molecular Mechanisms of Human Disease

Contact Information

Kim Boekelheide, MD PhD, 3-1783 (office), [email protected]

Overview

BIOL 2860 is designed for graduate students and focuses on the underlying causes of human disease. Students

should have a solid background in the life sciences with an understanding of the fundamental principles of

molecular biology, genetics, biochemistry and cell biology. The first half of the course will focus on cystic

fibrosis, using this disease to explore basic principles of molecular biology, genetics, physiology and pathology.

The second half of the course will center on benign prostatic hyperplasia and prostate cancer, using these

diseases to explore toxicology, the genetic and environmental basis of diseases, and carcinogenesis. A typical

class will consist of a lecture, individual student presentations and experimental planning exercises. Emphasis

will be placed on the development of presentation skills and research design. Readings will be assigned from

Robbins Basic Pathology (9th Edition), Junqueira Basic Histology Text & Atlas (14th Edition) (both available

online through the library website), primary literature, and reviews.

Objectives

The course objectives include:

Develop fundamental knowledge of the pathogenesis of human diseases

Provide familiarity with basic principles and utility of various analytical tools

Acquire basic skills in the use of the light microscope

Augment skills in oral presentation and the discussion of science and research

Practice planning of experiments to test specific hypotheses about disease states

Assessment

Students will be evaluated based on:

Class and microscope participation (10%)

Performance on individual in-class presentations (15%)

Performance on group in-class presentations (25%)

Written, in-class midterm exam (25%)

Written, in-class, non-cumulative final exam (25%)

Presentations

Individual in-class presentations: These presentations will occur in the second half of the semester and will be

based on assigned papers from published literature. These presentations will deal with topics current to the

subject of a particular class and will occur during that class. Dr. Boekelheide will meet with students at least a

week before their presentations to discuss specific items that will need to be covered during each presentation.

Presentations should take 10-15 minutes. Paper topics will be chosen midway through the semester.

Group in-class presentations: Group presentations will occur near the end of the semester. Presentations will

focus on various aspects of benign prostatic hyperplasia and/or prostate cancer. Possible topics include

endocrine disrupting chemicals and prostate diseases; biomarkers of benign prostatic hyperplasia and/or prostate

cancer; animal models of benign prostatic hyperplasia and/or prostate cancer; the concept of “latent” prostate

cancer; the meaning and consequences of “over-diagnosis” of prostate cancer; racial differences in the incidence

of benign prostatic hyperplasia and/or prostate cancer. Students may develop their own topic if they wish in

consultation with Dr. Boekelheide. Students will assemble into three to four groups with each group choosing

one topic for presentation. Each presentation will run 30 minutes with 10 minutes for questions. Presentations

can incorporate visual aids such as whiteboards and Powerpoint. Students will be required to consult with Dr.

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Boekelheide as they develop their presentation. Presentation topics and groups will be established midway

through the semester.

Work and Time Expectations for this Course

Over the 15 weeks of the semester, students will spend 3 hours per week in class with exceptions noted in the

schedule below (~38 hours total); 2 hours of lab time are scheduled for hands-on instruction in light

microscopy; and 2 hours are scheduled for a field trip to the Rhode Island Hospital Department of Pathology

and Laboratory Medicine. Homework and assigned reading is estimated at around 6 hours per week (~74

hours). Additional preparation time for the individual in-class presentation is estimated to be 10 hours, and

additional preparation time for the group in-class presentation is estimated to be 20 hours. There are two non-

cumulative exams, each of which is scheduled to last 3.0 hours and, for each, approximately 15 hours of review

is assumed.

Class Meetings

Throughout the semester, the class will usually meet twice each week for 1.5 hours each time. The two weekly

class meeting times will be determined at the initial organizational meeting for the course to be held at 70 Ship

St, Room 501A, on 9/7/16 from 1:15-2:45 PM.

First half of semester

Week 1 (9/5-9/9)

Organizational meeting

Short informal presentations by students on past research experiences (no powerpoints please!)

Discussion of goals and organization of class (topics, readings, presentations, exams, grading)

Selection of weekly class times

Sign up for basic skills sessions for the light microscope

Week 2 (9/12-9/16)

First class: Introduction/molecular basis

Robbins Basic Pathology, Chapter 6: Genetic and Pediatric Diseases, Genetic Diseases/Mendelian

Disorders: Diseases Caused by Single-Gene Defects/Diseases Caused by Mutations in Genes

Encoding Receptor Proteins or Channels/Cystic Fibrosis

Riordan et al. Identification of the cystic fibrosis gene: cloning and characterization of

complementary DNA. Science 1989;245:1066-72.

Cheng et al. Defective intracellular transport and processing of CFTR is the molecular basis of most

cystic fibrosis. Cell 1990;63:827-34.

Second class: Respiratory and gastrointestinal tracts—healthy! (Will be covered in two lectures)

Basic Histology, Chapter 1: Histology and Its Methods of Study; Introduction to Electron

Microscopy (pps. 1-9)

Basic Histology, Chapter 4: Epithelial Tissue; Characteristic Features of Epithelial Cells to

Transport Across Epithelia (pps. 71-88)

Basic Histology, Chapter 15: Digestive Tract; Introduction & General Structure of the Digestive

Tract & Small Intestine & Large Intestine (pps. 295-298, 314-326)

Basic Histology, Chapter 16: Organs Associated with the Digestive Tract; Introduction & Pancreas

& Liver (pps. 329-345)

Basic Histology, Chapter 17: The Respiratory System; Introduction & Nasal Cavities & Bronchial

Tree & Lung (pps. 349-351, 354-366)

Week 3 (9/19-9/23)

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First class: Respiratory and gastrointestinal tracts—healthy! (continued)

Second class: Respiratory, gastrointestinal and other tracts—diseased! (Will be covered in two lectures)

Robbins Basic Pathology, Chapter 1: Cell Injury, Cell Death, and Adaptations, Overview of Cellular

Responses to Stress and Noxious Stimuli-The Morphology of Cell and Tissue Injury

Rogers et al. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs.

Science 2008;321:1837-41.

Stoltz et al. Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs. J Clin

Invest 2013;123:2685-2693.

Submit anonymous written feedback and suggestions for improvement!

Week 4 (9/26-9/30)

First class: Respiratory, gastrointestinal and other tracts—diseased! (continued)

Second class: Nutrition/Experimental planning

BEFORE this class, research the following characteristics of cystic fibrosis and come prepared to

describe why they happen: failure to thrive; protein-calorie malnutrition; hypoproteinemia; edema;

fat-soluble vitamin deficiencies

Week 5 (10/3-10/7)

First class: Why is CF so common?/Modifiers of disease/Experimental planning

Pier et al. Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature 1998;393:79-82.

Gu et al. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature

2009;458:1039-42.

Second class: Treatment and prognosis (will be covered in two classes)

Yan et al. Ferret and pig models of cystic fibrosis: prospects and promise for gene therapy. Hum

Gene Ther Clin Dev 2015;26:38-49.

Bidou et al. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med

2012;18:679-88.

Holmes D. False dawn for cystic fibrosis disease modifiers? Nat Rev Drug Discov 2014;13:713-4.

Week 6 (10/10-10/14)

First class: (No class—holiday)

Second class: Treatment and prognosis (continued)

Week 7 (10/17-10/21)

Review/sample exam questions

Selection of individual and group in-class presentations for second half of semester

Possible topics/papers for individual in-class presentations:

Molecular basis of ……

Week 8 (10/24-10/28)

First class: midterm, 70 Ship St., rooms 105 and 106, 10/26, 11:30-2:30 PM

Students presenting following week meet with Dr. Boekelheide after class.

Second class: no class!

Slides and additional readings for classes in second half of semester will be posted this week.

Second half of semester

Week 9 (10/31-11/4)

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Overview of benign prostatic hyperplasia and prostate cancer, including clinical presentation, diagnosis,

epidemiology and pathology

Robbins Basic Pathology, Chapter 17: Prostate

Basic Histology, Chapter 21: The Male Reproductive System; Accessory Genital Glands (pps. 451-

456)

Student presentations

Students presenting next week meet with Dr. Boekelheide after class.

Week 10 (11/7-11/11)

Environmental diseases and basic principles of toxicology

Robbins Basic Pathology, Chapter 7: Introduction, Toxicity of Chemical and Physical Agents,

Environmental Pollution



Submit anonymous written feedback and suggestions for improvement

Week 11 (11/14-11/18)

First class: trip to Rhode Island Hospital; 11/16; meet in hospital lobby at 1 PM.

Second class: Endocrine disrupting chemicals and disease



Groups need to meet with Dr. Boekelheide by this week to go over presentations!

Week 12 (11/21-11/25)

First class: Models for studying prostatic diseases



Second class: holiday!

Week 13 (11/28-12/2)

First class: Models for studying prostatic diseases


Week 14 (12/5-12/9)

First class: Presentations by group A and B

o Group A:

o Group B:

Second class: Presentations by group C and D

o Group C:

o Group D:

Week 15 (12/12-12/16)

One class: Final exam! 70 Ship St., rooms 105 and 106, 12/14, 12:30-2:30 PM

Biology of the

Eukaryotic Cell

2016 Syllabus Biology 1050 / 2050

Prof. Ken Miller

Biology 1050 / 2050 2016 Syllabus Page 1

Biology 1050 / 2050

Biology of the Eukaryotic Cell Prof. Ken Miller

Lecture: Tues, Thur 1:00–2:20 Review: Thur 12–1 PM Seminars: Wed 12-1 PM

Description: Biology 1050 / 2050 is an advanced course which examines the organelles and macromolecular complexes of eukaryotic cells with respect to structural and functional roles in major cellular activities. It emphasizes the experimental basis for knowledge in modern cell biology using original literature, and discusses the validity of current concepts of cell structure and function.

Students: Biology 1050 / 2050 is intended for advanced undergraduates and beginning graduate students. It is complementary to BIOL 1270 and 1540. Expected Preparation: BIOL 0200, and at least one course in one of the following: biochemistry (e. g. BIOL 0280) cell biology (e. g. BIOL 0500), or genetics (e. g. BIOL 0470). Graduate students should register for BI 2050. Exams and Assignments: Two in-class exams will be given during the semester. At the end of the semester, students will prepare a research proposal related to one of the principal topics of the course. This proposal is considered part of the Final Exam. Expectations: The course will cover optical and molecular techniques in cell biology, functions of cellular compartments and organelles, and the organization and expression of genetic information in eukaryotes. Lectures and readings are based on current research in cell biology. Our principal expectation is that students will learn to read, analyze, and critique published research studies. Students are expected to master current conceptions and understanding of cellular structure and function, and also to propose an original research project that would advance those understandings. Time Commitments: Over 14 weeks, students will spend 39 hours in class (26 classes and seminars). Required reading for lectures and exam preparation are expected to take approximately 8 hours per week (112 hours). Writing the open book exam is expected to take approximately 12 hours. The written research proposal is expected to take at least 24 hours of literature research, experimental design, and writing.

• The final grade will be based upon performance as follows: Take Home Exam (October 11-18) 25% In-Class Exam (November 8) 25% Final exam (December 15): Research Proposal 17% Written Final 33%


Biology 1050 / 2050 Eukaryotic Cell Biology 2016 Schedule

Sept. 8 Introduction Miller 13 Optical Techniques in Cell Biology Miller 15 Molecular Techniques in Cell Biology Miller 20 Membranes Miller 22 Protein Targeting Miller 27 Ribosomes Gerwald Jogl 29 The Golgi Miller Oct. 4 Cellular Junctions Miller 6 Mitochondria Miller 11 Chloroplasts (take home exam) Miller 13 The Cytoskeleton Miller 18 Extracellular Matrix (take home collected) Miller 20 Apoptosis Miller 25 The Cell Cycle Miller 27 Mitosis Miller Nov. 1 The Genome Miller 2 Apoptosis & the ECM (MCB Seminar) Kim McCall (BU) 3 DNA Replication Miller 8 In Class Exam 10 Chromatin Miller 15 Centros-Telos Miller 17 Stem Cells Rich Freiman 22 Transcription Yiannis Savva (Brown) 24 Thanksgiving Holiday 29 RNA Processing Yiannis Savva (Brown) 30 Nuclear Envelope (MCB Seminar) Patrick Lusk (Yale) Dec. 1 Nucleo-Cytoplasmic Transport Miller 6 Signal Transduction Miller 8-12 Reading Period Dec 15 Final Exam (2 PM) Research Proposals due Class lectures: Tuesday and Thursday 1:00-2:20, room 291 BioMed Center Discussion Groups: Thursdays from 12-1 (in SFH rooms 130, 283, and 383)


The Biology 1050/2050 CANVAS course web site will contain contains copies of the lecture outline, powerpoint slides, reading list, any films and required research articles. This will be arranged in folders (“modules”) for each lecture, arranged by the date of the lecture. If you are registered for the course, you will be able to access the course site on CANVAS using the URL:

https://canvas.brown.edu/ We will provide hard copy handouts of the lecture outline, powerpoint slides and reading list in class for each lecture. Most assigned readings will be placed on "electronic reserve" at the Bio 1050/2050 CANVAS web site as Adobe Acrobat PDF files. We will not use CANVAS for E-mails or discussions. If you need to contact us, please do so using Brown g-mail and not via CANVAS. If you have questions about material from the lectures, you should first attend the weekly discussion session led by the TAs:

Discussion Groups: Thursdays from 12-1: 218 SFH & 283 SFH (UGrads)

Thursdays from 12-1: 383 SFH (grad students)

If you still have questions after that, see the course faculty member who gave the lecture for which you have questions:

Instructor:

[email protected] Sidney Frank Hall room 211 Office hours: Mon. 2:00-4:00

Teaching Assistants:

Graduate TA: Shen-Huan Liang

Undergrad TA: Kenneth Kim


HOW TO READ A SCIENTIFIC PAPER Abstract: What is the point the authors are trying to make?

(1) Do you want to read the paper further?

(2) Skim the end of the Introduction and Discussion to get more details on what was shown in the paper.

Introduction: What ideas are at stake?

(1) Gives the background of the field ---

mark the references you want to look up (2) The last paragraph summarizes the focus of the article Results --- the heart of the paper:

Do the results justify the claims and support the hypothesis?

(1) Do you believe the results claimed by the authors? First, look at the figures and figure legends – should be self-explanatory without

having to read the text.

(2) Then, read the accompanying text to see what the authors claim they have shown.

(3) Have the appropriate controls been done to rule out other hypotheses? Discussion How do the Results of this paper advance the concepts of the field?

(1) Summary of what they found

(2) Relevance

(3) Significance (4) Future directions

Methods

(1) Skim the methods sections to see what techniques were used.

(2) Read the methods more carefully IF you plan to repeat or extend the study

yourself


The MCB Seminar Series

2016

The Graduate Program in Molecular Biology, Cell Biology, and Biochemistry organizes a regular series of seminars. Two seminars are directly sponsored by Biology 1050 / 2050, as noted below and your attendance is required at those two seminars. However, nearly all of the MCB seminars will be relevant, in one sense or another, to the scientific questions that we cover in the course. Therefore, it makes good sense to attend (optional) the seminar series on a regular basis (check the schedule carefully — some seminars will be held at the LMM Auditorium at 70 Ship Street and others in room 220 Sidney Frank Life Science Building (SFH).

Fall 2015 MCB Graduate Program Seminars Sponsored by Bio 1050 / 2050:

Room 220 Sidney Frank Hall (required seminars)

Nov. 2 Kim McCall (BU) Apoptosis and the extracellular matrix Nov. 19 Patrick Lusk (Yale) Selective movement through the nuclear pore

A few other scheduled MCB Seminars

Oct. 5 Susan Gottesman (NIH) non-coding RNAs Oct. 19 Amy Wagers (Harvard) Regulation of stem cell function Oct. 26 Don Fox (Duke) Chromosomal Instability For updated information on the MCB Seminar Program, check the MCB Graduate Program’s web page.


Bio 1050/2050 Instructions for Research Proposal Component of the Final Examination

1. You are asked to design an original experiment that should answer a currently unsolved

specific problem related to material covered in this course on eukaryotic cell biology. This research proposal should not be the same as any past or present research project that you are working on, nor one you plan to begin. Do not choose a problem or an approach that necessitates making untested assumptions (e.g., use of a temperature-sensitive mutant which does not yet exist); the research involved should be able to be carried out today. It should involve a single experiment, not a project that will go on for years.

2. Your research proposal should include:

a. a statement of the specific problem or question to be solved on a topic covered in this course.

b. the name of the model system you choose (e.g., Drosophila polytene chromosomes, HeLa cells in culture, etc.), and defend this choice.

c. a statement of the experimental design (method of attack) and all necessary controls; the major methods used should have been covered in our course. (details about buffers, etc. not needed, but you should state what the methods are to be used - e.g., CsCl or sucrose gradient, Southern or Northern blot, specify what the probe is, etc.)

d. description of all possible results; avoid experiments most likely to give negative results (drawings of results may be helpful).

e. a discussion of the interpretations of all possible results. f. a brief discussion of the significance of solving the question (i.e., relationship to

previous research efforts, advancement of understanding, etc.)

3. You can confer with the staff and anyone else, with regard to formulating your proposal, but the basic idea must be your own.

4. Your research proposal will be evaluated on the basis of: originality, ingenuity and

cleverness, feasibility of experimental design, significance of the problem, lack of ambiguity in possible results, etc. It should be emphasized that you should ask a single specific question, rather than propose an extensive or ill-defined program of research.

5. Your research proposal should be typewritten, and must be no more than 3 pages

(including any diagrams). You may place a list of references on a fourth page. Full sentences are not obligatory - an outline format of presentation is fine, providing it is intelligible. This exercise counts as 1/3 of your final exam grade, and you must hand it in when you arrive for the final exam (no extensions!).

6. A few sample research proposals from previous years will be placed on reserve.

Proposals are due at the Start of the Final Exam


Biology 1050 / 2050 Biology 1050 / 2050 Textbook

(NOTE: This is a DRAFT copy of the syllabus. Since we are still considering another textbook, please do not purchase the Alberts textbook at this time. A final decision will be made by the end of June, 2016) Our textbook is the Sixth Edition of Molecular Biology of the Cell (Alberts et al, © 2015). There are various purchasing options, including an e-book version. You may use older editions of this book, but you will have to find corresponding pages for each reading assignment if you do.

While the bulk of our reading assignments will be drawn from original research papers and review articles, you will find the textbook useful in integrating topics covered in detail during the semester. The course may include assignments from the CD/ROM bundled with this text. Where possible, these will also be posted on the course web site.

The Sciences Library has a number of books documenting the history of Cell Biology: Carnoy, Jean B. La Biologie Cellulaire (1884) QH581 C4 Flemming, Walther Zellsubstanz, Kern, und Zelltheilung QH581 F57 Hertwig, Oskar Die Zelle und die Gewebe (1893-98) QH581 H57 The Cell (1895 translation) Wilson, Edmund, B. The Cell in Development & Inheritance QH581 W75 (1966 reprint of 1896 edition) Fawcett, Don The Cell (1981) QH582 F38 (A wonderful picture-book of electron micrographs) Brachet, Jean, & Alfred Minsky The Cell. Volumes 1-6 (1961-64) QH581 B64 (containing many key ideas from the early years of cell biology)


Mysteries of the Cell Science magazine published a special issue during the annual meeting of the American Society for Cell Biology: Science vol. 334: pp. 1046-1051 (2011). 2 Several articles in this issue are of special interest to Biology 1050/2050, especially a news focus article entitled “Mysteries of the Cell” (Science 334: 1046-1051). A copy of the article is on the course web site, and is optional reading for our first class on September 10th.

While we won’t be able to address each of the mysteries described in the article during the semester, you’ll find that it gives a hint of just how much we have yet to learn in our study of the most basic units of living things.

BIOL1310/2310 DEVELOPMENTAL BIOLOGY FALL 2016

Lecture: Tuesday/Thursdays 9 – 10:20AM, Lecture: BMC 081 Lab: Wednesdays 1:00 – 4:50PM, Room BMC B11

INSTRUCTOR:

Kristi A. Wharton: Room 370, Sidney Frank Hall Office Hours: by appointment

[email protected]

TEACHING ASSISTANTS: Megan Gura: [email protected] Audrey Lee: [email protected]

COURSE MATERIAL: Lectures – Lecture slides will be posted on the course Canvas site. Readings - Lectures will be supplemented with readings in the required text (Gilbert & Barresi, Developmental Biology, Eleventh Edition (Sinauer, 2016)) and from primary literature. Electronic versions (pdfs) of the primary literature reading assignments will be posted on the course Canvas site. Movies & other Media – periodically videos of developing embryos, experimental

procedures, or tutorials will be assigned to enhance and/or supplement lectures.

Laboratory Exercises – The laboratory is a major component of this course. Students will keep a digital laboratory notebook using Microsoft OneNote to document experimental design, observations, results, and conclusions. A file describing the lab will be available on the course Canvas site prior to each lab.

REQUIRED TEXT: Developmental Biology, 10e, by Scott F. Gilbert (Sinauer 2013)

The hardbound book is available in the Brown Bookstore. GRADING OPTION: BIOL1310 ABC/NC or S/NC (student choice) BIOL2310 ABC/NC PREREQUISITES:

This course is intended for intermediate to advanced undergraduate and graduate students. The minimum prerequisites for this course are a year of introductory biology and one additional biology course beyond the introductory level. For the latter, a course in genetics, cell & molecular biology, biochemistry, or embryology provide the most useful background.

COURSE REQUIREMENTS: BIOL1310 (undergraduate students)

1. Regular attendance in lecture, laboratory and designated discussion sessions. 2. Participation in lecture, laboratory and discussion sessions. 3. Completion of assigned reading. 4. Satisfactory completion of written and oral assignments. These include:

Laboratory notebook: Students will be keeping a digital laboratory notebook documenting the purpose of each experiment, the experimental design, methods, results and interpretation of the results. (100pts) Use of animal embryos in the laboratory follows regulations of the Animal Welfare Act.

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Quizzes: Seven short 10’ quizzes will be given in class to help both students and faculty

assess each student’s understanding of material presented in lecture. Six out of seven quizzes will count towards the final grade. (60pts)

Exams: Two exams will be held on Monday, Oct 3 & Oct 31, at 7pm. Students can drop the lowest grade. (100pts) The third exam will be held Wednesday Dec 7 at 2pm. (120pts)

Final student presentation: As a culmination of our study of developmental biology we will hold a BIOL1310/2310 symposium the week after Thanksgiving break. Students will choose and research a topic or question in developmental biology that has not been specifically covered in lecture, and present an oral report to the class as a whole (80pts) Choice of topic REQUIRES faculty consultation and approval by Nov 15th!

Attendance and Participation (40pts) COURSE REQUIREMENTS: BIOL2310 (graduate students)

Course requirements for graduate students are the same as for undergraduates with two exceptions. Participation in laboratory exercises is welcomed and encouraged for graduate students but optional. The final oral presentation should address its topic in more depth and be a more extensive critical analysis.

COURSE GOALS

1. To familiarize students with the subject matter of developmental biology, including basic concepts and experimental analysis. Developmental biology is a broad, highly interdisciplinary field and we will not attempt a comprehensive survey of all its aspects. Instead, representative topics have been selected to illustrate fundamental concepts.

2. To encourage students to place the "facts" that they learn into an appropriate operational and theoretical framework.

3. To enable students to learn the limitations and transient nature of "facts" - that is, to understand the design and context of experiments which lead to the establishment of something as a fact - and to develop an ability to evaluate such experiments in a rigorous, critical fashion.

4. To enhance student appreciation of the living embryo by means of laboratory exercises.

ACADEMIC ACCOMMODATIONS Students seeking accommodations due to a disability or medical condition should contact Student and Employee Accessibility Services and for those seeking psychological support services please contact Counseling and Psychological Services.

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WEB SITES

The BIOL1310/2310 site can be reached at canvas.brown.edu. It will include the syllabus, lecture presentations, assigned papers, links to other sites, etc. Below is a list of some links to useful sites. If you find others you think are relevant to the course, please let us know.

http://www.devbio.com/ - Your textbook's website. Very useful and informative with links to Vade Mecum and Dev Tutorials.

http://www.sdbonline.org/ - This site has many links to other sites of interest, such as The Interactive Fly, the Developmental Biology Cinema, the Developmental biology Virtual Library

http://www.luc.edu/depts/biology/dev.htm - Bill Wasserman's page, lots of links to model

organisms. http://www.ucalgary.ca/UofC/eduweb/virtualembryo/ - Leon Browder's site with a useful tutorial http://www.stanford.edu/group/Urchin/ani-plus.htm - Nice animations, especially useful for the

first sea urchin lab.

http://flybase.bio.indiana.edu/ - A database of the Drosophila genome with images, references, and links to other useful sites.

http://zfish.uoregon.edu/ - Also known as "The Fish Net". All about zebrafish. http://worms.zoology.wisc.edu/frogs/welcome.html - An amphibian development tutorial. http://www.med.unc.edu/embryo_images - Scanning electron micrographs of normal and

abnormal mammalian development, mostly mouse, some human

http://www.xenbase.org/index.html - Xenopus site – check out atlas, movies, fate maps http://zygote.swarthmore.edu/index.html http://www.ambystoma.org/AGSC/axolotl.htm Site with info on axolotls with pictures of developmental stages http://www.uoguelph.ca/zoology/devobio/splab4/index.htm - Early chick development http://www.sciencedaily.com/

http://www.indiana.edu/~anat550/embryo_main/index.html - Human embryology Animations http://www.visembryo.com/ - The Visible Embryo – focus on human development https://embryology.med.unsw.edu.au/embryology/index.php/Main_Page http://www.pbs.org/wgbh/nova/odyssey/clips/ http://origamiembryo.cba.arizona.edu/video.cfm

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COURSE SCHEDULE

Lec Date Topic

1 Sept 8 Scope of course / Principles of experimental embryology

2 Sept 13 Developmental potential/Stem cell concept

Sept 14 Techniques and methodologies used to study development

How to keep a research lab notebook

3 Sept 15 Fertilization: Sperm-egg interaction

4 Sept 20 Egg activation & early cleavage (quiz)

Sept 21 Lab I – Fertilization and early development: Sea Urchin

5 Sept 22 Regulation of early cleavage/Localized factors

6 Sept 27 Cytoplasmic determinants & Specifying asymmetries (quiz)

7 Sept 28 Establishing body axes

NOTE: This lecture will occur on Wednesday

8 Oct 29 Constructing a segmental body plan: gene regulatory cascade

Oct 3 EXAM I (Lectures 1-8) 7pm

9 Oct 4 Elaboration of the segmental body plan: Homeotic selector genes

Oct 5 Lab IIA – Pattern formation: Mutant phenotypes in Drosophila embryos

10 Oct 6 Drosophila DV patterning & Establishing vertebrate DV axis

11 Oct 11 Early vertebrate development (quiz)

Oct 12 Lab IIB – Pattern formation: Gene expression in Drosophila embryos

12 Oct 13 Vertebrate patterning: The organizer

13 Oct 18 Bird/Mammal development & Hox regulation (quiz)

Oct 19 Lab III: Induction and axis specification:

Early vertebrate development in the Axolotl

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14 Oct 20 Neurulation & neural patterning A/P & D/V

15 Oct 25 Somitogenesis & Specification of paraxial mesoderm (quiz)

Oct 26 Lab IV: Vertebrate patterning: Zebrafish development

Oct 27 No Class

Oct 31 EXAM II (Lectures 9-15) 7pm

16 Nov 1 Neural Crest

17 Nov 2 Ectodermal placodes: eye development

18 Nov 3 Lateral plate mesoderm: formation of the heart field and vessels

19 Nov 8 Establishing the vertebrate limb: Organizing zones (quiz)

Nov 9 Lab V: Organogenesis: Chick development

20 Nov 10 Sex determination & hormonal control of development

21 Nov 15 Stem cell niches & iPSCs (quiz)

22 Nov 16 Regeneration

Lab VI: Regeneration: Planaria/Hydra

23 Nov 17 Convergence of environmental influences on development

24 Nov 22 Molecular control of evolutionary diversification

Nov 23-27 Happy Thanksgiving

Nov 29 Student Topic Presentations

Nov 30 Student Topic Presentations

Dec 1 Student Topic Presentations

Dec 6 Review

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Dec 7 EXAM III (Lectures 16-24) 2pm

BIOL2030 FOUNDATIONS FOR ADVANCED STUDY IN THE LIFE SCIENCES

Fall 2016

INSTRUCTORS

Alison DeLong SFH 166

Alison_DeLong @Brown.edu Telephone: 3-3888

Mark Johnson

SFH 160 [email protected]

Telephone: 3-3556

Art Salomon LMM 335

[email protected] Telephone: 401-323-9648

John Sedivy

LMM 435 [email protected]

Telephone: 3-7631

Office hours for all instructors are by appointment. COURSE MEETINGS Lectures and Discussion Sections (see Lecture Schedule) SFH218 Monday, Tuesday, Thursday: 9:00-10:20 AM Friday: 10:15 – 11:35 COURSE CONTENT BIOL2030 is a graduate-level course focused on multidisciplinary approaches to biological questions. The mechanisms and regulation of basic cellular processes involving nucleic acids (synthesis, structure, maintenance and transmission) and proteins (synthesis, maturation, function) and integration of those processes into more complex circuits (signaling, cell cycle control, development) will be presented through examples from the primary scientific literature. COURSE OBJECTIVES The primary goal of this course is to develop skills for both critical reading of the primary literature and for effective presentation of hypotheses, data and interpretation. Students who successfully complete the course should be able to

1. understand major advances in the analysis of basic cellular processes and the integration of those processes into more complex circuits

2. understand the concept of burden-of-proof in the experimental disciplines of cell biology, genetics, biochemistry and developmental biology

3. evaluate and discuss the strengths and weaknesses of a wide range of experimental approaches and their application to the analysis of biological phenomena in diverse model systems

4. lead and participate in critical discussions of current primary literature 5. communicate in writing and via oral presentation the importance of specific

publications in the context of current scientific knowledge

BIOL2030 -- Fall 2016

COURSE MATERIALS All course materials and grades will be posted to the BIOL2030 Canvas website (https://canvas.brown.edu/courses/1070333). Both pdfs and links to online publications will be posted, and assigned reading will be posted at least a week in advance of each lecture. Lecture notes will be posted shortly before each class meeting, and printed copies will be available. There is no textbook for BIOL2030. REGISTRATION AND PREREQUISITES BIOL2030 is an advanced course in experimental biology intended for beginning graduate students; it is required for Ph.D. students in the MCB Graduate Program. All other students must obtain instructor permission, and enrollment is limited to graduate students. There are no prerequisites for this course. COURSE REQUIREMENTS

1. Attendance and participation in ALL lecture and discussion sections 2. Reading assignments, completed before the lecture or discussion section

meeting 3. Written and oral assignments:

a. Problem sets The two problem sets will require students to apply their knowledge to hypothetical scientific observations. Students will be asked to formulate hypotheses to explain the observations, develop experimental approaches to test these hypotheses, and/or discuss the possible outcomes and interpretations.

b. Mid-term exams Two take-home exams will be administered, each preceded by a designated study day. Exams will be due in hard copy format 8 hours after posting on the course website.

c. Cumulative final exam A cumulative final exam will be preceded by a reading week and review sessions. Students will have one and one-half days to complete the final exam.

d. Presentations/Discussions Each student will organize one 30-minute presentation focused on current work of an upcoming MCB seminar speaker and will lead a discussion on this work. Discussion Section meetings will include 2 presentations per session. All students will be required to submit discussion questions prior to Discussion Section meetings, and will be graded on participation in the discussions.

e. Mini-review essay Each student will write a mini-review essay based on an assigned paper from the BIOL2030 reading list. Students will select one of the assigned papers from the course reading list as the starting point for a mini-review; the instructor assigning that paper will be responsible for approving the student’s choice of topic. After the topic is approved, each student will write a 1500- to 2000-word mini-review with an annotated bibliography. The expectation is that 6 – 12 of the primary references will provide the core findings discussed in the review.

BIOL2030 -- Fall 2016

COURSE-RELATED WORK EXPECTATIONS Over 14 weeks, students will spend an average of 4 hours per week in class meetings (lectures and discussion sections; 56 hours total). Specific out-of-class time investments will vary for individual students, but required reading is expected to take a minimum of 12 hours per week (168 hours), and additional work (two problem sets, preparation of a Discussion Section presentation, researching and writing a mini-review) will require approximately 5 additional hours per week (70 hours). Students will also submit two 8-hr take-home midterm exams for which approximately 12 hours of study (each) are assumed, and a take-home final exam for which 16 hours of work and approximately 24 hours of study are assumed (80 hours total). GRADING SUMMARY

Assignment Point Value

2 Midterm Exams (125 ea.) 250 2 Problem Sets (100 ea.) 200

Discussion Section 150 Mini-review essay 150

Final Exam 250 TOTAL 1000

Grading Option: ABC/NC

Projected Final Grade Assignments

100-85% A 84-75% B 74-65% C

Below 65% NC LATE POLICY All due dates will be clearly specified on the course schedule. Assignments must be turned in on time in the format specified to be eligible for full credit. Assignments turned in late will lose points on the following scale: up to 24 hours, 15% of assignment value; 24 – 48 hours, 50% of assignment value; more than 48 hours, no credit. We encourage you to turn in your work on time. ACCESSIBILITY AND ACCOMMODATIONS: Brown University is committed to full inclusion of all students. Please inform an instructor early in the term if you have a disability or other conditions that might require accommodations or modification of any of these course procedures. For more information, please contact Student and Employee Accessibility Services (https://www.brown.edu/campus-life/support/accessibility-services/) at 401-863-9588 or [email protected].

BIOL2030 -- Fall 2016

EXPECTATIONS FOR ACADEMIC HONESTY We refer you to the guidelines set forth by the dean of the college regarding academic honesty as a general overview of our expectations for BIOL2030: http://brown.edu/academics/gradschool/academic-code Expectations specific to BIOL2030:

1. Students may work together in discussion and consultation on the problem sets, but all submitted assignments must be the exclusive written work of the student indicated on the submitted material.

2. All submitted materials must be appropriately referenced. The verbatim transfer of information from published works must be avoided. All references to published work must be fully cited with author, title, source (including page numbers) and date.

3. Students may not collaborate or consult with fellow students or other persons in the completion or submission of written examinations. Students may use lecture notes, handouts and slides and the assigned papers as resources during exams, but may not consult other publications or online resources.

Topic Instructor Day DateCourse Introduction/organization DeLong Th 8-SepNo class meeting - Discussion Section research day F 9-Sep

L1 Introduction to Transcription/Initiation DeLong M 12-SepDiscussion Section Organizational Meeting DeLong M 12-Sep

L2 Transcriptional Elongation DeLong T 13-SepMCB Seminar: Barry Ganetzky W 14-Sep

L3 Transcription: Cycling and Coupling DeLong Th 15-SepL4 mRNA Surveillance DeLong F 16-SepL5 Cellular Transformation Sedivy M 19-SepL6 Replicative Senescence Sedivy T 20-Sep

MCB Seminar: Utz Herbig W 21-SepL7 Stem Cells: Totipotency and Differentiation Sedivy Th 22-Sep

PS1 Problem set 1 posted at 5PM F 23-SepL8 Apoptosis Sedivy F 23-SepD1 Discussion M 26-SepL9 Translation introduction/initiation Salomon T 27-Sep

MCB Seminar: W 28-SepL10 Translation elongation/peptide bond formation Salomon Th 29-SepL11 Translation termination Salomon F 30-SepPS1 Problem set 1 due at 9AM M 3-OctD2 Discussion M 3-OctL12 Protein structure and function Salomon T 4-Oct

MCB Seminar: Susan Gottesman W 5-OctL13 Protein Processing Sedivy Th 6-OctL14 Enzymology of Protein Destruction Sedivy F 7-Oct

Fall holiday - No class meeting M 10-OctExam 1 Lectures 1-14 9 am - 5 pm T 11-Oct

MCB Seminar: W 12-OctL15 Protein folding principles Salomon Th 13-OctL16 Assisted protein folding Salomon F 14-OctD3 Discussion M 17-OctL17 Small RNAs DeLong T 18-Oct

MCB Seminar: Amy Wagers W 19-OctL18 Molecular Genetics of Development DeLong Th 20-OctL19 Asymmetric Cell Divisions in Development Johnson F 21-OctD4 Discussion M 24-OctL20 Germ Cells and Sex Determination DeLong T 25-Oct

MCB Seminar: Don Fox W 26-OctL21 Introduction to Cell Structure and Molecular Trafficking DeLong Th 27-OctL22 Dynamics of Nuclear Localization DeLong F 28-OctPS2 Problem set 2 posted at 5PM F 28-OctD5 Discussion M 31-OctWrit Mini-review consult day - No class meeting T 1-Nov

MCB Seminar: Kim McCall (BIOL1050/2050) W 2-NovL23 Quality Control in the Secretory Pathway DeLong Th 3-NovL24 Receptor-Ligand Interactions DeLong F 4-NovPS2 Problem set 2 due at 9AM M 7-NovD6 Discussion M 7-NovL25 Receptor-Coreceptor cooperation Salomon T 8-Nov

MCB Seminar: Huntington Willard W 9-NovL26 System-level analysis of cell signaling Salomon Th 10-NovL27 Signal transduction to the Nucleus Salomon F 11-Nov

BIOL2030 Syllabus 2016

No class meeting (study day) M 14-NovExam 2 EXAM 2 Lectures 15-27 9 am - 5 pm T 15-Nov

MCB Seminar: W 16-NovL28 Introduction to the Cell Cycle: Checkpoints DeLong Th 17-NovL29 DNA Replication DeLong F 18-NovL30 Chromosome Cohesion and Segregation DeLong M 21-NovL31 Molecular Motors and the Cytoskeleton Sedivy T 22-Nov

Thanksgiving break-no class W-Th-F Nov. 23 - 25Writ Mini-review due in class M 28-NovL32 Intro to Chromatin Sedivy M 28-NovL33 Establishing Chromatin Structure Sedivy T 29-Nov

MCB Seminar: Patrick Lusk (BIOL1050/2050) W 30-NovL34 Maintaining Chromatin Domains Sedivy Th 1-DecL35 Genome Stability and DNA Repair Sedivy F 2-DecL36 Genome Engineering Johnson M 5-DecL37 Genome Sequencing Sedivy T 6-Dec

MCB Seminar: Michael Bonaguidi W 7-DecReview sessions M 12-Dec

Final Exam Final Exam W-Th 12/14 - 12/15

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SCIENTIFIC COMMUNICATION BIOL2150 Fall 2016

INSTRUCTORS: Judith Bender Office: SFH162 Tel: 3-6238 e-mail: [email protected] Kimberly Mowry Office: SFH268 Tel: 3-3636 e-mail: [email protected] FIRST COURSE MEETING: Friday, September 9, 2015, noon-3:30 pm – SFH 350 Section 1 (Judith Bender) SFH350 Section 2 (Kimberly Mowry) SFH218 COURSE CONTENT: BIOL2150 is a graduate-level course focused on the effective dissemination of scientific information through distinct modes of written and oral communication. Through practical examples of activities common to the profession (writing a grant proposal and presenting research work orally), students will develop the skills necessary to effectively communicate scientific ideas, experiments, and results. Each of the activities will be dissected into key components that will be individually developed with the aid of interactive discussions and peer review. In addition, students will develop documents to describe their research experiences and motivations. COURSE GOALS

1. To develop effective written and oral communication skills for the exchange of scientific information.

2. To introduce students to the goals of each of the various modes of scientific communication and to explore the complementary nature of these modes.

3. To deconstruct scientific communications into component parts, to highlight the essential contributions of each part, and to facilitate the preparation of the completed product.

4. To develop an appreciation of the invaluable contribution of peer review to the scientific process.

RECOMMENDED TEXTS (available in SFH230): “The Craft of Scientific Writing” Michael Alley “The Craft of Scientific Presentations” Michael Alley “The Elements of Style” William Strunk Jr. and EB White

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REGISTRATION AND PREREQUISITES: BIOL2150 is a course in scientific communication intended for advanced biology graduate students who are engaged in dissertation research projects. Registration requires instructor permission. COURSE REQUIREMENTS: 1. Attendance at all course meetings, individual instructor meetings, and the weekly MCB Graduate Program seminar series (Wednesdays noon-1 pm). 2. Participation in lectures, peer reviews, and discussions. 3. Written assignments must be posted to the course Canvas site by 3 pm on the indicated due date:

a. Seminar Blog: Students will enter critiques of the MCB Graduate Program weekly seminar presentations onto the course Canvas site by 3 pm on the Thursday after each Wednesday seminar. Through this exercise, students will develop an awareness of the attributes of an effective presentation, including delivery, organization, level of detail and slide aesthetics. The discussion of the seminar from the previous week will be reviewed at the beginning of each class. b. Personal Statement/Research Experience: Working with the instructors over several drafts, students will develop a 3-page essay describing the personal, educational, professional, and research experiences that have shaped their scientific interests and career goals. c. NSF-style Research Proposal: Students will prepare a 2-page research proposal through a series of assignments starting with the development of a logical outline for the experimental plan. The NSF-style research proposal assignments will be peer reviewed for organization, clarity, and effectiveness and then revised. d. NIH-style Research Proposal: Students will expand their 2-page NSF-style research proposal to a 7-page (1 aims page + 6 page proposal) NIH-style research proposal. The NIH research proposal will first be reviewed by the instructors, and then be peer reviewed for organization, clarity, and effectiveness. e. Peer Review Critiques: Students will provide peer review of research proposal projects through written critiques based on NIH-style grant reviews.

4. In-class oral assignments: a. Oral Presentation: Students will develop a 10-minute oral/slide show presentation on their research proposal projects, explaining the major question in the field, the approach taken to address this question, and potential outcomes of the work. The presentation will be peer reviewed for aesthetics, organization, clarity, and effectiveness, and then revised. b. Elevator Pitch: Students will prepare a two-minute oral (no slides/visual aids) “elevator pitch” that highlights the key aspects of their own research proposal projects. Students will also prepare a two-minute elevator pitch on the research proposal project of a classmate assigned by the instructors. c. Peer Review Critiques: Students will orally present their written peer review critiques of research proposals.

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EXPECTATIONS FOR ACADEMIC HONESTY Students must follow the guidelines set forth by the Dean of the College regarding academic honesty: http://www.brown.edu/Administration/Dean_of_the_College/academic_code/code.html Expectations specific to BIOL2150:

1. Students should discuss their work with others including the instructors and the thesis advisor while developing the organization of the written documents and slide show presentations. However, each student’s submitted assignments must be his/her exclusive written work or slide design.

2. All submitted materials must be appropriately referenced. The verbatim transfer of information from published works should be avoided. All references to published work must be cited with sufficient information to allow unambiguous identification of the reference.

GRADING OPTION: ABC/NC LATE ASSIGNMENT POLICY: Assignments turned in by 3:30 pm of the due date = no penalty Assignments turned in by midnight of the due date = reduced half a grade (for example, a B assignment would receive a B-) Assignments turned in by 3 pm the day following the due date = reduced a full grade (for example, a B assignment would receive a C) Assignments turned in more than one day late = no credit

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GRADING SUMMARY

Assignment Value Due Date MCB Seminar Blog 100 (total for all

blogs combined) Every Thursday after a seminar

Personal Statement/Research Experience

First Draft 50 9/29 Second Draft 75 10/10 NSF-Style Research Proposal Experimental Plan Logic Tree 1 50 9/19 Experimental Plan Logic Tree 2 75 9/26 Proposal First Draft 100 10/3 Proposal Second Draft 150 10/10 Complete NSF-Style Application

Third drafts of both essays 150 10/17 NIH-Style Research Proposal

Proposal First Draft 100 11/14 Proposal Second Draft 200 12/5

Oral Presentations First Draft 50 11/4, 11/11 Second Draft 100 11/18

Third Draft 150 12/2 Elevator Pitches 50 12/16 Peer Review/Discussions

Practice Critique Logic Tree 1 0w + 0o* 9/22 + 9/23 Critique of Logic Tree 2 25w + 25o 9/29 + 9/30 Critique of NSF Proposal 1 25w + 25o 10/6 + 10/7

Critique of NSF Proposal 2 25w + 25o 10/13 + 10/14 Critique of NIH Proposal 2 25w + 25o 12/8 + 12/9

Total 1500 *w = written, o = oral

FINAL GRADE ASSIGNMENTS

100-85 % A 84-75 % B 74-65 % C

Below 65 % NC

BIOL2150 SCIENTIFIC COMMUNICATION Syllabus - Fall 2016

Week Date Activity 1 F 9/9 Lecture: Course intro/Intro to scientific writing/Fellowship proposals (JB) 2 M 9/12-F 9/16

W 9/14 Th 9/15 F 9/16

Meet with thesis advisor and instructors to discuss the logic tree MCB Graduate Program Seminar (B. Ganetzky) Blog on MCB Seminar Lecture: The peer review process/preparing critiques (JB) Discussion: Research project rationales

3 M 9/19 W 9/21 Th 9/22 F 9/23

Logic Tree Draft 1 MCB Graduate Program Seminar (U. Herbig) Practice written bullet point critiques of Logic Tree Draft 1 Blog on MCB Seminar Practice peer review: Logic Tree Draft 1

4 M 9/26 W 9/28 Th 9/29 F 9/30

Logic Tree Draft 2 MCB Graduate Program Seminar (TBA) Written bullet point critiques of Logic Tree Draft 2 Personal Statement/Research Experience (PS/RE) Draft 1 Blog on MCB Seminar if scheduled Peer review: Logic Tree Draft 2 (schedule TBD due to D. Berg defense)

5 M 10/3 W 10/5-F 10/7 W 10/5 Th 10/6 F 10/7

NSF-style Research Proposal Draft 1 Meet with instructors to discuss first draft of PS/RE MCB Graduate Program Seminar (S. Gottesman) Written bullet point critiques of NSF-style Research Proposal Draft 1 Blog on MCB Seminar Peer review: NSF-style Research Proposal Draft 1

6 M 10/10 W 10/12 W 10/12- F 10/14 Th 10/13 F 10/14

PS/RE Draft 2 NSF-style Research Proposal Draft 2 No MCB Graduate Program Seminar (Yom Kippur) Meet with instructors to discuss second draft of PS/RE Written bullet point critiques of NSF-style Research Proposal Draft 2 Peer review: NSF-style Research Proposal Draft 2

7 M 10/17 W10/19-F10/21 W 10/19 Th 10/20 F 10/21

Complete NSF-style application (Research Proposal and PS/RE) Meet with instructors to discuss complete NSF-style application MCB Graduate Program Seminar (A. Wagers) Blog on MCB Seminar Lecture: Oral/Slide Presentations (KM)

8 M 10/24 W 10/26 Th 10/27 F 10/28

NSF Applications Due MCB Graduate Program Seminar (D. Fox) Blog on MCB Seminar Lecture: NIH-style proposals and data presentation (KM; JB away)

9 W 11/2 Th 11/3 F 11/4

MCB Graduate Program Seminar (K. McCall) Blog on MCB Seminar Oral/slide presentation: Group A Draft 1

10 W 11/9 Th 11/10 F 11/11

MCB Graduate Program Seminar (H. Willard) Blog on MCB Seminar Oral/slide presentation: Group B Draft 1

11 M 11/14 W 11/16 Th 11/17 F 11/18

NIH-style Research Proposal Draft 1 (JB comments by W 11/23) MCB Graduate Program Seminar (TBA) Blog on MCB Seminar if scheduled Oral/slide presentation: Draft 2

12 W 11/23 THANKSGIVING BREAK 13 W 11/30

Th 12/1 F 12/2

MCB Graduate Program Seminar (P. Lusk) Blog on MCB Seminar Oral/slide presentation: Draft 3 with Sheridan Center advising

14 M 12/5 W 12/7 Th 12/8 F 12/9

NIH-style Research Proposal Draft 2 MCB Graduate Program Seminar (M. Bonaguidi) Written bullet point critiques of NIH-Style Research Proposal Draft 2 Blog on MCB Seminar Peer Review: NIH-Style Research Proposal Draft 2

15 F 12/16 2 minute “Elevator pitch” talks about your own project and the project of a classmate with peer discussion

Expected Hours Week Class + Seminar Out of Class 1 3.5 + 0 0 2 3.5 + 1.0 Research project rationale preparation = 0.5

Logic Tree 1 discussion with advisor and instructors = 0.5 Seminar Blog = 0.5 Logic Tree 1 = 6.0 PS/RE 1 = 2.0

3 3.5 + 1.0 Bullet point critiques on Logic Tree 1 = 3.0 Seminar Blog = 0.5 Logic Tree 2 = 4.0 PS/RE 1 = 2.0

4 3.5 + 0 Bullet point critiques on Logic Tree 2 = 3.0 PS/RE 1 = 4.0 NSF Research Proposal 1 = 8.0

5 3.5 + 1.0 Bullet point critiques on NSF Research Proposal 1 = 3.0 Instructor meetings on PS/RE 1 = 0.5 Seminar Blog = 0.5 NSF Research Proposal 2 = 6.0 PS/RE 2 = 6.0

6 3.5 + 0 Bullet point critiques on NSF Research Proposal 2 = 3.0 Instructor meetings on PS/RE 2 = 0.5 NSF Complete Application (Research Proposal 3 + PS/RE 3) = 8.0

7 3.5 + 1.0 Instructor meetings on Complete Application = 0.5 Seminar Blog = 0.5

8 3.5 + 1.0 Seminar Blog = 0.5 Oral/Slide presentation 1 = 6.0

9 3.5 + 1.0 Seminar Blog = 0.5 Oral/Slide presentation 1 Group A = 0.3 NIH Research Proposal 1 6.0

10 3.5 + 1.0 Seminar Blog = 0.5 Oral/Slide presentation 1 Group B = 0.3 NIH Research Proposal 1 = 6.0

11 3.5 + 0 Oral/Slide presentation 2 = 8.0 12 0 + 0 NIH Research Proposal 2 = 6.0

Oral/Slide presentation 3 = 6.0 13 3.5 + 1.0 Seminar Blog = 0.5

NIH Research Proposal 2 = 6.0 14 3.5 + 1.0 Bullet point critiques on NIH Research Proposal 2 = 6.0

Seminar Blog = 0.5 15 3.5 + 0 Elevator Pitches = 2.0 Total 57.0 123.0

FALL 2015 !

BIOL2340 Neurogenetics and Disease

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A critical evaluation of current research papers in neurogenetics and disease conducted in seminar/discussion format. Expected: Advanced course in cell biology, molecular biology, or genetics. For graduate students and qualified undergraduates (with permission). Enrollment is limited. !

First Class: Wednesday, Sept. 9, 2015 Sidney Frank Hall 383 4:00 - 6:50pm

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Instructors: Eric Morrow MD PhD

Robert Reenan PhD For more information email: [email protected]

[email protected]

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Neurogenetics and Disease - BIOL2340-S01 Classroom: SFH 383 from 4:00 - 6:50pm, Wednesdays

Course Syllabus INSTRUCTORS

Eric Morrow MD PhD: Room 337, Laboratories for Molecular Medicine (LMM) Office Hours: by appointment; LMM (70 Ship Street) or SFH 270 Telephone: 863-9778 Email: [email protected]

Rob Reenan PhD: Room 372, Sidney Frank Hall (SFH)

Office Hours: by appointment Telephone: 863-6353 Email: [email protected]

COURSE DESCRIPTION Study of genetic mutations provides a powerful approach to dissect complex biologic problems. In this course, we will focus on fascinating discoveries from “forward genetic” studies – moving from nervous system phenotype to genetic mutation discovery. There will be an emphasis on neurologic disease phenotypes and the use of novel genomic methods to elucidate the central molecular and cellular causes for these conditions. In addition, the course will emphasize the use of “reverse genetics” – engineered mutations in model systems – to dissect nervous system function and disease mechanisms. Disorders to be covered include neurodevelopmental as well as neurodegenerative disorders. These include autism, intellectual disability, schizophrenia, epilepsy, amyotrophic lateral sclerosis, Parkinson disease, Alzheimer’s disease and/or other conditions. A variety of genetic and cellular mechanisms will be discussed, including: rare and common sequence variation, copy number variation, trinucleotide repeats, epigenetic mechanisms, mechanisms of neuronal morphogenesis, mechanisms of protein trafficking and protein turnover, and mechanisms of cell signaling. The powers of novel methodologies in neurogenetics will be elucidated, including: high-throughput sequencing, transgenic methods in model organisms and patient-derived induced pluripotent stem cell technologies. Major themes include the heterogeneity of brain disorders and mechanisms of neuronal dysfunction. Critical themes will emerge, including: learning from rare, extreme phenotypes vs. sporadic, “common” forms of the disorders; understanding key gaps in knowledge, including the gene-circuit gap and the circuit-behavior gap; and finally mechanisms as potential therapeutic targets. Limited to 20 students.

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COURSE MATERIALS Required Reading: Primary and review journal articles assigned by lecturers (see course schedule for details). Electronic versions of required reading documents will be provided through Brown University My Courses (https://mycourses.brown.edu). All papers are also available through PubMed (http://www.ncbi.nlm.nih.gov/pubmed). GRADING OPTIONS ABC/NC or S/NC (student choice) PREREQUISITES BIOL2340 is taught at an appropriate level for graduate students or advanced undergraduate students. The prerequisites for this course are that students have previous course experience in genetics, molecular biology, cell biology and/or introductory neurobiology. COURSE EXPECTATIONS AND LOGISTICS

1. Regular attendance in class. 2. High degree of participation in paper discussions (600 points). 3. Completion of assigned reading. 4. Satisfactory evaluation on assignments, which are the following:

• “News and Views”. Students will be expected to turn in one two-page summary of a paper to be specified by instructors in the style of a Nature “News and Views”. We have assigned several examples of such articles as reviews throughout the course. We recommend that you try to read these examples prior to writing your own. The article should contain the following information concisely stated:

1. Context/Background: What was known in the field or about the problem at the time of the experiments?

2. Experimental Question: What is the question or set of questions to be addressed in the study?

3. Methods/Approach: What experimental approaches did the investigators take to address the questions? What were the controls?

4. Results: What were the essential findings in the study? 5. Interpretations: What were the authors’ conclusions

regarding their data? Do the data meet the burden-of-proof to make the stated claim?

6. Strengths/Weaknesses: What makes the findings strong? What are the caveats or weakness?

7. Importance: Why are the findings and conclusions important? What makes the findings strong? What are the caveats or weakness? This paper should include references at the level required for science writing. In brief, if data are referenced and/or a claim is made, the primary source needs to be provided to support the data/claim. It is not sufficient to reference a review article that makes reference to the claim, instead,

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the reference that includes the primary support needs to be given.This assignment will be scored out of 100 points. This year the News and Views assignment will be on the following paper:

! Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006 Jun 29;441(7097):1162-6.

The primary research paper that is the subject of the News and Views will be discussed in the 9th class, and the assignment will be due at 4pm on the day prior to class. No late papers will be accepted.

• Molecular Techniques Assignment. Students will choose a molecular technique

that is used in primary papers. Each student in the class will work on a distinct technique from other students such that a comprehensive list across the class will be developed. Each student will write one-half to one full page with illustrations as necessary (in a Word document format) that illustrates:

1. When/why do we use the given technique? 2. How does the technique work? 3. What may be some expected results and how do we

interpret the data? 4. What are the strengths and weaknesses of the approach?

Please email this assignment to Dr. Morrow and Dr. Reenan prior to the 4th class at 4:00pm. This assignment will be scored out of 50 points. The student will be expected to be an expert in the given technique as these techniques are used in papers over the course of the semester.

• “Your disease-of-interest assignment”. Students should choose a disease that

interests them and/or may choose a disease that will be discussed in class. For their chosen disease/disorder, students will write one page (in a Word document format) that describes:

1. Epidemiology/prevalence 2. Age of onset/course of disease 3. Symptoms 4. Physical findings 5. Clinical laboratory findings 6. Prognosis 7. Pathology/autopsy findings 8. Pathophysiology 9. Treatment

Please email this assignment to Dr. Morrow and Dr. Reenan by the 5th day of class prior to 4:00pm. This assignment will also be scored out of 50 points. The

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student will be expected to be an expert in the given disease/disorder as the topic arises over the course of the semester.

• Final papers. The students will complete a 5-page paper, double-spaced. They

will select two primary papers. The first paper will be one in which a gene mutation is discovered or associated with a given phenotype or disease. The second paper will involve a study in an experimental system, perhaps a model organism, wherein some aspect of the function of the gene or protein is elucidated. The student will be expected to cover the essentials of the topic as in the “News and Views”, but in greater depth. That is, for each paper they should cover: background, questions, experiments, results, interpretation, strengths, and weaknesses. Students are expected to work with course instructors to choose the two papers that are the topics of their written work. Students are required to communicate to Dr. Morrow and Dr. Reenan the titles of the specific two publications prior to Thanksgiving break. After discussion with the instructors, the instructors may guide the student to alternative but related publications. The Final Paper will be evaluated based on the choice of publications, the critical review of the studies, and the clarity of the discussion regarding the scope and importance of the findings. This assignment will be scored out of 200 points.

Total Scores: News and Views 100 points Molecular Technique 50 points Disease Outline 50 points Final Paper 200 points Class Discussion 600 points Total 1000 points

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COURSE PHILOSOPHY Students will be guided through a tapestry of genetics concepts, disease mechanisms, and model systems. Students can expect to be challenged in this course by the scope and amount of material. However, the course is structured such that student attendance and participation will ensure that the pace of the class is appropriate to master the material. Students will be asked questions in class in the form of discussion and should not interpret the dialogue as being tested. Instructors will use student feedback to facilitate the effective navigation through the course material. The instructors are expected to provide a thought-provoking frame for the paper discussions and to stimulate class discussion to foster an interactive, dynamic environment. The students are expected to read the papers thoroughly in advance of the class. The material in the course will cover a scope that is likely beyond a student’s prior knowledge. The students are expected to read the primary papers as well as make a substantial effort to research background material and methods in order to understand the primary papers in sufficient depth for discussion. For each session, there is a review paper listed; however, further work with references within the primary text and/or other literature research may be necessary for the student to prepare for discussions. The instructors do not expect students to have a full mastery of critical reading in neurogenetics at beginning of the term. Developing excellence in skills in reading the literature and expert knowledge will be a life-long process! A greater effort prior to each class with each primary paper will allow the student to make the most of the discussion, and most importantly, to develop skills as a critical reader of the scientific literature over the semester. Instructors will focus most on trajectory of the student over the term with regard to the student’s contribution to the discussion. The instructors encourage students to work together in small groups and to meet in small groups to discuss papers in advance of class.

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Biol2340-S01 Course Schedule and Lecture Topics Lecture: Wednesday 4:00-6:50pm

Sidney Frank Hall 383

Date Faculty Topic 1 Sept. 9 EM/RR Scope of course/concepts; Administrative issues 2 Sept. 16

RR Amyotrophic lateral sclerosis (ALS) (Part 1): genetics and

biochemistry 3 Sept. 23

(Yom Kippur) RR ALS (Part 2): TDP43 -- Case study of gene and

mechanisms in ALS 4 Sept. 30 EM/RR Neurodevelopmental Disorders: Rett syndrome, MeCP2

in transcriptional regulation of brain development – relevance to autism ! Molecular Techniques assignment due prior to class, 4pm via email

5 Oct. 7 EM/RR Neurodevelopmental Disorders: Molecular mechanism in human brain growth and neocortical development, ASPM ! Disease-of-interest assignment due prior to class, 4pm via email

6 Oct. 14

RR Somatic cell mutation – Gene mechanisms without inheritance

7 Oct. 21 EM/RR Schizophrenia – Neurodevelopmental or neurodegenerative? Course adjustment form distributed and returned prior to end of class

Special Lecture

Oct. 28 Noon SFH 220 Dr. Serge Przedborski, Columbia University

8 Oct. 28 EM/RR Neurodegeneration: What is the role of glia? With Special Guest Dr. Serge Przedborski

9 Nov. 4

RR Neurodegeneration: Parkinson Disease – Approaches to function (Drosophila) ! News and Views assignment due prior to 4pm

10 Nov. 11 EM/RR Neurodegeneration: Tau-opathy – Cellular and in vivo studies

11 Nov. 18 EM/RR Neurodevelopmental Disorders: Autism – Human genetics and induced pluripotent stem cell models

Nov. 25 (Thanksgiving)

No Session – Thanksgiving Break

12 Dec. 2 EM/RR From fly to human 13 Dec. 9

(Reading Period) Final Paper due by 9am; Please email to Dr. Morrow and

Dr. Reenan

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Biol2340-S01 Neurogenetics and Disease

SELECTED READING MATERIAL

Intro Session 1. Scope of course/concepts:

! Faculty- led discussion ! Pescosolido MF, Sabbagh M, Yang U, Morrow EM. Lighting a path: genetic studies

pinpoint neurodevelopmental mechanisms in autism and related disorders. Dialogues Clin Neurosci. 2012 Sep;14(3):239-52.

Session 2. Amyotrophic lateral sclerosis (ALS) (Part 1): genetics and biochemistry Review Paper

! Renton AE, Chiò A, Traynor BJ. State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci. 2014 Jan;17(1):17-23.

Papers for discussion ! Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC,

Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008 319, 1668–1672.

! Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006 Oct 6;314(5796):130-133.

Session 3. ALS (Part 2): TDP43 -- Case study of gene and mechanisms in ALS Review Paper

! Lee EB, Lee VM, Trojanowski JQ. Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat Rev Neurosci. 2011 Nov 30;13(1):38-50.

Paper for Discussion ! Ling JP, Pletnikova O, Troncoso JC, Wong PC. NEURODEGENERATION. TDP-43

repression of nonconserved cryptic exons is compromised in ALS-FTD. Science. 2015 Aug 7;349(6248):650-5.

Session 4: Neurodevelopmental Disorders: Rett syndrome, MeCP2 in transcriptional regulation of brain development – relevance to autism Review Paper

! Zoghbi, HY. Rett syndrome: what do we know for sure? Nat Neurosci. 2009 Mar;12(3):239-40.

Paper for Discussion ! Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY. MeCP2, a key

contributor to neurological disease, activates and represses transcription. Science. 2008 May 30;320(5880):1224-9.

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Session 5. Neurodevelopmental Disorders: Molecular mechanism in human brain growth and neocortical development, ASPM Review Paper

! Fish JL, Dehay C, Kennedy H, Huttner WB. Making bigger brains-the evolution of neural-progenitor-cell division. J Cell Sci. 2008 Sep 1;121(Pt 17):2783-93.

Papers for Discussion ! Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K,

Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG. ASPM is a major determinant of cerebral cortical size. Nat Genet. 2002 Oct;32(2):316-20.

! Pulvers JN, Bryk J, Fish JL, Wilsch-Bräuninger M, Arai Y, Schreier D, Naumann R, Helppi J, Habermann B, Vogt J, Nitsch R, Tóth A, Enard W, Pääbo S, Huttner WB. Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline. Proc Natl Acad Sci USA. 2010 Sep 21;107(38):16595-600.

Session 6. Somatic cell mutation – Gene mechanisms without inheritance Review Paper

! Poduri A, Evrony GD, Cai X, Walsh CA. Somatic mutation, genomic variation, and neurological disease. Science. 2013 Jul 5;341(6141):1237758.

Paper for Discussion ! Poduri A, Evrony GD, Cai X, Elhosary PC, Beroukhim R, Lehtinen MK, Hills LB, Heinzen

EL, Hill A, Hill RS, Barry BJ, Bourgeois BF, Riviello JJ, Barkovich AJ, Black PM, Ligon KL, Walsh CA.Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron. 2012 Apr 12;74(1):41-8.

! Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K, Gage FH. L1 retrotransposition in neurons is modulated by MeCP2. Nature. 2010 Nov 18;468(7322):443-6.

Session 7. Schizophrenia – Neurodevelopmental or neurodegenerative? Review Paper

! Flint J, Munafò M. Schizophrenia: genesis of a complex disease. Nature. 2014 Jul 24;511(7510):412-3.

*This paper is a Nature News and Views and may serve as one example for the News and Views writing assignment. Papers for Discussion

! Mohn AR, Gainetdinov RR, Caron MG, Koller BH. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell. 1999 Aug 20;98(4):427-36.

! Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014 Jul 24;511(7510):421-7.

Session 8. Neurodegeneration: What is the role of glia? Papers for Discussion

! Re DB, Le Verche V, Yu C, Amoroso MW, Politi KA, Phani S, Ikiz B, Hoffmann L, Koolen M, Nagata T, Papadimitriou D, Nagy P, Mitsumoto H, Kariya S, Wichterle H, Henderson CE, Przedborski S. Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron. 2014 Mar 5;81(5):1001-8.

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! Le Masson G, Przedborski S, Abbott LF. A computational model of motor neuron degeneration. Neuron. 2014 Aug 20;83(4):975-88.

Session 9. Neurodegeneration: Parkinson Disease – Approaches to function (Drosophila) Review Papers

! Verstraeten A, Theuns J, Van Broeckhoven C. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era. Trends Genet. 2015 Mar;31(3):140-9.

! Marsh JL, Thompson LM. Drosophila in the study of neurodegenerative disease. Neuron. 2006 Oct 5;52(1):169-78.

Papers for Discussion ! Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M.

Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006 Jun 29;441(7097):1162-6.

! Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005 May;8(5):657-63.

Session 10. Neurodegeneration: Tau-opathy – Cellular and in vivo studies Review Paper

! Frost B, Götz J, Feany MB. Connecting the dots between tau dysfunction and neurodegeneration. Trends Cell Biol. 2014 Aug 26. pii: S0962-8924(14)00119-6. doi: 10.1016/j.tcb.2014.07.005. [Epub ahead of print]

Papers for Discussion ! Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK, Pitstick R, Carlson GA,

Lanier LM, Yuan LL, Ashe KH, Liao D. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron. 2010 Dec 22;68(6):1067-81.

! Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007 Feb 1;53(3):337-51. Erratum in: Neuron. 2007 Apr 19;54(2):343-4.

Session 11. Neurodevelopmental Disorders: Autism – Human genetics and induced pluripotent stem cell models Review Papers

! Guilmatre A, Huguet G, Delorme R, Bourgeron T. The emerging role of SHANK genes in neuropsychiatric disorders. Dev Neurobiol. 2014 Feb;74(2):113-22.

! Paşca SP, Panagiotakos G, Dolmetsch RE. Generating human neurons in vitro and using them to understand neuropsychiatric disease. Annu Rev Neurosci. 2014;37:479-501.

Papers for Discussion ! Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren

G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007 Jan;39(1):25-7.

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! Shcheglovitov A, Shcheglovitova O, Yazawa M, Portmann T, Shu R, Sebastiano V, Krawisz A, Froehlich W, Bernstein JA, Hallmayer JF, Dolmetsch RE. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature. 2013 Nov 14;503(7475):267-71.

Session 12. From fly to human Review Paper

! Todorovic V. Flies give wings to human disease studies. Nat Methods. 2014 Dec;11(12):1197.

Papers for Discussion ! Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W,

Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LE, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014 Sep 25;159(1):200-14.

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U:\BioMed_Shared\DOGradStud\_RCR Course\RESPONSIBLE CONDUCT IN RESEARCH TRAINING\RESPONSIBLE CONDUCT IN RESEARCH 2016\RCR_FALL_2016_SCHEDULE_AND_SYLLABUS.doc

Responsible Conduct in Research (RCR) Training ~ Fall 2016 ~

Required for entering PhD students in Division of Biology and Medicine

Meeting Times: Tuesdays from 4-6 PM (Sept 20 – Nov 1, 2016) Location: MACMILLAN HALL – ROOM 115

Course Leaders: Elizabeth O. Harrington, PhD Associate Dean, Office of Graduate & Postdoctoral Studies Justine J. Allen, PhD Training Grant Manager, Office of Graduate & Postdoctoral Studies

Graduate Teaching Assistant (Google Documents & case discussion leader): Maggie Watson, PhD candidate, Pathobiology

Admin Contact: Tracey Cronin, Office of Graduate and Postdoctoral Studies, 863-3281

TEXT BOOK: The ORI Introduction to the Responsible Conduct of Research by Nicholas H. Steneck, updated Edition 2007

web version or pdf @ https://ori.hhs.gov/sites/default/files/rcrintro.pdf

x Overall Goals: The overall goal of this course is to review and discuss what research or scientific misconduct is and the impact unethical conduct can cause within and outside of the research community. Topics to be covered include:

¡ Animal research ¡ Human subject research ¡ Proper representation of data ¡ Original presentation of data/ plagiarism ¡ Authorship ¡ Mentorship ¡ Conflict of interest ¡ Confidentiality ¡ ‘Whistle-blowing’ ¡ Copyright ¡ Intellectual Property ¡ Data Management and Sharing Plan ¡ Individual Development Plan ¡ Rigor & Reproducibility ¡ Collaborative Science btw Academia and Outside Researchers

x Expectations: Requirements to earn certificate of completion:

¡ Attendance/participation in 7 sessions ¡ Completion of assignments ¡ Passing grade on final exam (>75%) ¡



Speaker and Topic Schedule

9/20/16: “Essentials of Research Misconduct and Policies Presenter: Justine J. Allen, PhD, Training Grant Manager/ Maggie Watson

¾ Overview of training, readings, IDP, videos, googlesite ȡȱWhat is Scientific Misconduct? � Office of Scientific Integrity � You and the Brown Academic Code � Handling misconduct

o ��ȱȡȱ��

Assignment Due 11/1/16: Complete your online Individual Development Plan (IDP).

9/27/16: “Overview of Mentoring” Presenter: Kimberly Mowry, PhD, Professor of Medical Science, Chair of Molecular Biology, Cell Biology, and Biochemistry

¾ Expectations and Responsibilities of Mentor and Mentee ȡȱConflict Resolution ȡȱProfessionalism

“Human Subjects Research” Presenter: Presenter: Jerome Sanes, PhD, Professor of Neuroscience

¾ Safe and Ethical Research � The checkered history � Regulations � The complex decisions � IRB � What, Where, and How

10/4/16: “ Plagiarism and Publications”

John Sedivy, PhD, Professor of Medical Science, Department Molecular Biology, Cell Biology, and Biochemistry

¾ What is plagiarism? � Authorship � Publications � Peer Review

Presenter: Hope Lappen, MLIS, Biomedical & Life Sciences Librarian ¾ Author’s rights � Copyright � Intellectual Property

“Conflict of Interest”

Presenter: Anatoly Zhitkovich, PhD, Professor of Medical Science, Department of Pathology & Laboratory Medicine

¾ What this means for you as a student and for your faculty mentor



10/11/16: “Research Involving Animals” Presenter: Diane Hoffman-Kim, PhD, Associate Professor of Medical Science, Department of Molecular Pharmacology, Physiology, & Biotechnology

¾ Overview � Past problems � Regulations � Activists � How does this relate to your research now OR later?

“Data Reproducibility/ Rigor” Presenter: Diane Lipscombe, PhD, Professor of Medical Science, Department of Neuroscience

¾ Overview � Scientific integrity � Accountability � Social responsibility � Transparency � Biological variables � Key scientific resources � How does this relate to your research now OR later?

10/18/16: “Data Management/ Big Data”

Presenter: Neil Sarkar, PhD, Associate Professor of Medical Science, Director for the Ctr for Biomedical Informatics

¾ How do you store and organize large data sets? � Are these data sets useful for others beyond the people in your own lab?

“Data Sharing/ Data Management” Presenter: Andrew T. Creamer, MAEd, MSLIS, Scientific Data Management, Brown University Library

¾ ��ȱ��ȱ��ȱ��ȱ��ȱ��ȱ��ȱȡȱ��ȱ��ȱ��¢ȱ��ȱ��ȱȡȱ��ȱ��ȱ��ȱ��ȱȡȱ��ȱ��ȱ��ȱ��ȱ��ȱ��ȱȡȱ��ȱ��ȱ��ȱ�� ȡȱ�ength of time the data needs to be stored after the grant is over, PI leaves, paper published, etc.

10/25/16:

“Collaborative Science with academia and industry” Presenter: Edith Mathiowitz, PhD, Professor of Medical Science, Department of Molecular Pharmacology, Physiology, & Biotechnology

¾ Intellectual property � technology transfer � patents � Bayh-Dole Act � issues with publishing work � materials transfer agreements (MTA)

“Case Studies/ Review” Presenter: Elizabeth Harrington, PhD/ Maggie Watson

¾ Preparation for final exam.

11/1/16: Final Exam



Note: The successful completion of “Responsible Conduct in Research Training” is a requirement for your PhD training, federal training grants and fellowship awards. A Certificate of Completion will be e-mailed by end of the semester to each student who attends all sessions of this class, completes assignments and passes the final exam (score of 75 or higher). ********************************************************************************************************** To contact Office for Graduate & Postdoctoral Training:

Phone: 863-3281; e-mail [email protected]

TA:

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Biol1270/Biol2270: Advanced Biochemistry Semester of Fall 2016

Course Syllabus

INSTRUCTORS: Asst. Prof. Alexandra Deaconescu (x3215; LMM128), [email protected] Prof. Rebecca Page (x6076; LMM127), [email protected] ENROLLMENT: The course is open to both undergraduates and graduate student (graduate students will register for Biol2270). Expected previous coursework includes BIOL0280, CHEM0330, CHEM0350, CHEM0360. CLASS MEETINGS: There will be two meetings per week, scheduled Tue/Thu 2:30-3:50pm. TA sessions to be announced. MEETING LOCATION: Biomed Center 081 OFFICE HOURS: Prof. Deaconescu, by appointment and Friday, 10-11:30 am Prof. Page, by appointment COURSE DESCRIPTION AND GOALS: Throughout the course, we will go beyond textbook information on selected topics in modern biology (see Course Lecture Schedule) and will instead focus on the critical analysis of basic research papers that have contributed mechanistic insights into a variety of biological processes, ranging from DNA replication and transcription to the regulation of the cytoskeleton and the unfolded protein response. Papers will be presented in terms of background and significance, hypothesis, experimental methods, data quality and interpretation in order to convey to the students, among others, the necessity for cross-validation in biological research.

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Thus, our goals are:

• To convey to students the major advances in our understanding of basic cellular processes from a biochemical perspective

• To introduce students to a wide range of experimental techniques and their applications to modern biochemical analysis through critical evaluation of published literature

• To familiarize students with primary literature and the burden of proof in scientific experimentation. In particular, students will develop a keen awareness of the biases inherent to experimental approaches and the resulting need to consider multiple interpretations for any given result.

COURSE REQUIREMENTS:

• Lecture attendance and participation (50 pts) • Reading assignments, completed before course meetings • Written and oral assignments:

! Exams: Two in-class exams (100 pts. each) and one cumulative final exam (150 pts.)

! Presentation: Students will give one oral presentation (100 pts) describing one of the methods used in the papers covered throughout the semester. Method selected requires approval of the instructors.

! Study guide: Students will be required to write one study guide for one of the semester lectures. This should include background information critical for understanding the papers assigned, the questions asked, a brief summary of the experimental approach and the key findings. Students are also asked to formulate, based on the papers covered by the study guide, one outstanding question in the field and briefly explain how they might address it experimentally.

TIME COMMITMENT: Over 14 weeks, students will spend 39 hours in class (20 lectures + 3 class + periods assigned to oral presentations + 3 exams). The required reading for lecture and exam preparation will take an additional 8 hours per week (112 hours). Writing the study guide is expected to take about 6 hours and preparation for the oral presentation (reading, research and slide preparation) an additional 24 hours. GRADING: Biol1270 Biol2270 Exam 1 100 pts 100 pts Exam 2 100 pts 100 pts Final 150 pts. 150 pts. Oral Presentation 75 pts. 75 pts. Study Guide 25 pts. 25 pts. Class Participation 50 pts. 50 pts.

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PROJECTED GRADE GUIDELINES: Biol1270 Biol2270 A 85-100 90-100 B 85-75 80-89 C 65-74 70-79 NC <65 <70 EXPECTATIONS FOR ACADEMIC HONESTY We refer students to the Brown University Academic Code: https://www.brown.edu/academics/college/degree/sites/brown.edu.academics.college.degree/files/uploads/Academic-Code.pdf

• Students may (should!) work together in discussion and consultation on the reading and understanding of the papers, but all submitted assignments must be the exclusive written work of the student indicated on the submitted material.

• Students may not collaborate with or consult with other students in the completion or submission of written examinations.

COURSE LECTURE SCHEDULE Lecture Date Faculty Topic

1 Sep 8 Deaconescu Introduction to the Course – Methodology and Experimental Design

2 Sep 13 Page Biochemistry Refresher and Introduction to Structure-Function Relationships

3 Sep 15 Page Co-translational Protein Folding 4 Sep 20 Page Post-translational Protein Folding 5 Sep 22 Page Prokaryotic Protein Turnover 6 Sep 27 Page Eukaryotic Protein Turnover 7 Sep 29 Page Unfolded Protein Response I 8 Oct 4 Page Unfolded Protein Response II 9 Oct 6 Deaconescu DNA Replication Oct 11 Midterm 1 (lectures 1-8)

10 Oct 13 Deaconescu Tour of the Structural Biology Labs at Brown 11 Oct 18 Page CLIP 12 Oct 20 Deaconescu RNA Polymerases – Central Enzymes of Gene

Expression 13 Oct 25 Deaconescu DNA Repair: Links to Transcription 14 Oct 27 Deaconescu Chromatin Remodeling 15 Nov 1 Deaconescu Regulation of the Cytoskeleton

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16 Nov 3 Guest Speaker Prof. Radhika Subramanian: Microtubules Nov 8 Midterm 2 (lectures 9-15)

17 Nov10 Deaconescu Two Component Systems

18 Nov 15 Deaconescu RNA Turnover 19 Nov 17 Deaconescu RNA Interference 20 Nov 22 Deaconescu Crispr/CAS

Nov 24 No class Thanksgiving Recess 21 Nov 29 Deaconescu Preparation for Oral Presentations 22 Dec 1 Oral Presentations I by Students 23 Dec 6 Oral Presentations II by Students Dec 8 No class Reading Period Dec 19 Final Exam (all lectures) The BIOL1270/2270 CANVAS site will contain pdf files of the lectures as well as the reading material. OTHER COURSE ACTIVITIES Students will have the opportunity to tour the Deaconescu Laboratory and the Structural Biology Facility located at LMM 70 Ship St. Students will learn and observe how recombinant proteins are produced, purified and crystallized for structural determination efforts, and will also learn about the sophisticated instruments employed in these processes, including chromatography systems, crystallization robots, X-ray diffractometers and NMR magnets. Students can even grow their own protein crystals and then observe them under the microscope! The tour will take place on October 13 and will be led by Prof. Deaconescu and Prof. M. Clarkson, Manager of the Brown Structural Biology Facility. This activity is required and not optional.!

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THE MCB SEMINAR SERIES 2016

Students are encouraged (but not required) to attend the seminar series organized by the Graduate Program in Molecular Biology, Cell Biology and Biochemistry. Please note that some of these seminars are held at Sidney Frank Hall (room 220), while others at the LMM Auditorium at 70 Ship St. While some of these seminars have little thematic overlap with topics discussed in class, they will provide a good perspective by leading scientists on how to approach and dissect a scientific problem. Listed below are the upcoming seminars scheduled for the Fall semester:

9/14 MCB Graduate Program Seminar

Dr. Barry Ganetzky, University of Wisconsin

12 PM SFH 220


Dr. Utz Herbig, Rutgers University

12 PM LMM 107


Dr. Susan Gottesman, National Institutes of

Health

12 PM LMM 107


Dr. Amy Wagers, Harvard University

12 PM LMM 107


Dr. Don Fox, Duke University

12 PM SFH 220


Dr. Kim McCall, Boston University

12 PM SFH 220

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Dr. Huntington Willard, Marine Biological

Laboratory

12 PM LMM 107


Dr. Patrick Lusk, Yale University

12 PM SFH 220


Dr. Michael Bonaguidi, University of Southern

California

12 PM LMM 107

Molecular Biology & Chemistry BIOL2000X: Current topics in Functional Genomics Course Directors: Dr. Erica Larschan/ Dr. Nicola Neretti Course Information Semester, Year: Fall 2016 Meeting day, time: TBD Meeting Location: TBD Organizational Meeting: TBA Course Description A technological revolution in genomics has exponentially increased our ability to gather biological data. A host of new methods and types of analysis has arisen to accommodate this dramatic shift in data collection. The broad scope of inquiry has ushered in an era of “system-wide” approaches and brute-force strategies where rare signals can be detected and studied. In this seminar we will cover papers that embody this new approach. Background Preparation (Prerequisites) Students are encouraged to review background material relevant to each class. Students typically have taken an advanced undergraduate-level course in biology. Texts and Journal References

The craft of scientific presentation (Michael Alley) The elements of style (Strunk and White) Primary Readings from the literature

Course Learning Outcomes By the end of this course, students will be able to: • Discuss how the genome is regulated within a two and three-dimensional context • Understand how to choose the correct technology to answer your biological question • Learn how to give effective oral presentations Course Requirements & Assignments • Students will be expected to read all of the assigned primary literature before the class and to be ready to discuss the papers in depth with their peers.

• Students will be responsible for several oral presentations during the course (number to be determined after the first meeting), in which they present an assigned paper, with appropriate research into background material. Well-organized, well-prepared presentations which incorporate the techniques outlined in the ‘craft of scientific presentation’ are expected. Presentations will be evaluated by the course leaders. • Students will be responsible for preparing a scientific research poster on a topic approved by the course instructors. It will be evaluated for writing, figures and presentation. Grading • Class participation 20% • Oral presentations 50% • Poster Presentations 30% How participation and presentations will be evaluated. Class participation: students are expected to have read the assigned papers before class; they are expected to be able to answer questions (orally) about the papers and also be active participants in class discussions. Students will be evaluated on the level of participation and the insightfulness of the comments/questions Oral presentations: students will give lectures on assigned readings (typically 1-2/course, but this is dependent on the course enrollment). Students are evaluated (equally) on: a) organization of the presentation/slides, b) quality of the slides, c) oral delivery and d) knowledge of the material. Poster presentations: Students will also prepare posters on a topic of their choosing which will propose new experiments based on the paper presented in one of their oral presentations. Posters are evaluated for: a) organization and clarity in the text, especially the abstract, b) quality of the figures and c) oral presentation of the poster to their peers and course instructors

Letter Grade Description Learning Outcome

A Complete mastery of course material and

additional insight beyond course material

Insightful

B Complete mastery of course material Proficient

C

Gaps in mastery of the course material; not at the level expected of a Brown University

student

Developing

NC

Inability to demonstrate mastery of any course

material of unethical standards of academic

conduct

Ineffective

All classes must be attended to complete the class, unless specific permission is granted for an absence by the course director. Unapproved absence or late attendance may result in a lower grade being assigned. Scientific and Professional Ethics The work you do in this course must be your own. Feel free to build on, react to, criticize, and analyze the ideas of others but, when you do, make it known whose ideas you are working with. You must explicitly acknowledge when your work builds on someone else's ideas, including ideas of classmates, professors, and authors you read. If you ever have questions about drawing the line between others' work and your own, ask the course professor who will give you clear guidance. Lectures

Week Lecture Papers

0 Organizational Meeting

1 Introduction to Functional Genomics

Lecture: Neretti/Larschan

2 Genome Biology Paper 1: The ENCODE Project Consortium, "An integrated encyclopedia of DNA elements in the human genome", Nature 489, 57–74, 2012 Paper 2: Prufer et al., "The complete genome sequence of a Neanderthal from the Altai Mountains", Nature 505, 43–49 (02 January 2014) Paper 3: The 1000 Genomes Project Consortium, "An integrated map of genetic variation from 1,092 human genomes", Nature 491, 56–65 (01 November 2012)

3 Single cell genomics Review: Clark et al., “Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity”, Genome Biology201617:72 Paper 1: Buenrostro et al., “Single-cell chromatin accessibility reveals principles of regulatory variation”, Nature 523, 486–490 (23 July 2015) Paper 2: Gaublomme et al., “Single-Cell

Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity”, Cell. 2015 Dec 3;163(6)

4 Metagenomics Review: Wooley et al. “A Primer on Metagenomics”, Plos Comp Bio 2010. Paper 1: Claesson et al., “Gut microbiota composition correlates with diet and health in the elderly”, Nature 488, 2012. Paper 2: Vlaminck et al., “Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy”, Cell 155, 2013

5 The 3D architecture of the genome

Review 1: Gibcus et al., “The hierarchy of the 3D genome.”, Mol Cell. 2013 49(5). Review 2: Dekker et al. “Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data.”, Nat Rev Genet. 2013 Jun;14(6) Paper 1: Naumova et al. “Organization of the mitotic chromosome.”, Science. 2013 Nov 22;342(6161).

6 Transcription Factor Networks

Paper 1: Davidson et al. “A Genomic Regulatory Network for Development.” Science. 2002. 295:1669. Paper 2: Fuxman Bass et al. “Human Gene-Centered Transcription Factor Networks for Enhancers and Disease Variants” Cell. 2015 161:661.

7 Long non-coding RNAs

Paper 1: Quinn et al. “Rapid evolutionary turnover underlies conserved lncRNA-genome interactions.” Genes and Dev. 2016. 30:191. Paper 2: Sauvageau et al. Multiple knockout mouse models reveal lincRNAs are required for life and brain development. 2013. eLife.

8 Bivalent chromatin domains

Paper 1: Bowman et al. “H3K27 modifications define segmental regulatory domains in the Drosophila

bithorax complex” 2014. ELife. Paper 2: Bernstein et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells: Cell. 2006.

9 Epigenetics Paper 1: Greer et al. “DNA methylation on N6 adenine in C. elegans” 2015. Cell: 161:868. Paper 2: Gimelbrant et al. “Widespread monoallelic expression on human autosomes” 2007. Science. 318:1136.

10 Poster Conference

Posters prepared by students on a topic of their choice and presented to one another in a single meeting

Credit Hours: 180 Total Hours In class time: 30 hours Preparing for two hour-long oral presentations: 20 hours Preparing poster for final conference day and meeting with instructor about poster: 30 hours Reading primary scientific papers preparing for class discussion each week: 100 hours

https://canvas.brown.edu/courses/957884/files/46577299/download?wrap=1




Introduction to MCB Faculty Research(Faculty on Parade) Fall 2016

Sidney Frank Hall room 218 DayTime

Day Date Time Speaker and Title

Thurs Sept 8 12:00

12:30

Shipra Vaishnava –Host-microbe interaction at the intestinal mucosa Nicolas Fawzi –Atomic details of RNA-binding proteins inside membraneless organelles associated with cancer and ALS

Tues Sept 13 12:00

12:30

Louis Lapierre – Transcriptional regulation of autophagy and longevity Nicola Neretti – Genomic instability in aging and age-

associated diseases Thurs Sept 15 12:00

12:30

Kristi Wharton – Adventures in studying the mechanisms

underlying intercellular signaling in development and disease

Tues Sept 20 12:00

12:30

Erica Larschan - X marks the spot: Dosage compensation in Drosophila

Gary Wessel - How to make a germ-line stem cell ... the mother (and father) of all stem cells

Thurs Sept 22 12:00

12:30

Richard Bennett - Fungal sex and pathogenesis Karla Kaun - Understanding memory and addiction using Drosophila

Tues Sept 27 12:00

12:30

Christopher de Graffenried – Cytoskeletal

Morphogenesis in Trypanosoma brucei Gilad Barnea - trans-Tango: Transsynaptic Mapping and

Manipulation of Neural Circuits

Thurs Sept 29 12:00

12:30

Alexandra Deaconescu – Alison DeLong - One Signal, Two Circuits: How Protein Phosphatase 2A Controls Ethylene Synthesis

Tues Oct 4 12:00 12:30

Johh Sedivy – Why do we grow old and can we do anything about it? Kimberly Mowry – RNA Transport: Motors and Messages

Thurs Oct 6 12:00

12:30

Alexander Jaworski - Development and organization of

neural circuits William Fairbrother –

Tues Oct 11 12:00

Laurent Brossay - Tissue specificity of NK cell responses to

MCMV infection

Gerbi – no Padbury – no Salomon – no Chen – no Oancea – no Page – no Connors - no

12:30 Walter Atwood - Molecular and cellular biology of human

polyomaviruses

Thurs Oct 13 12:00

12:30

David Rand - Evolutionary genetics of mitochondrial fitness

and aging in Drosophila Thomas Bartnikas – Molecular Basis of Manganese Transport in Mammals

Tues Oct 18 12:00

12:30

Peter Belenky – Antibiotics and Microbial Communities

Judith Bender - Gene regulatory networks in plants

Thurs Oct 20 12:00

12:30

Anne Hart - A doubleheader: Neurodegeneration and Sleep

Ashley Webb - Preserving neural stem cells during aging

Tues Oct 25 12:00

12:30

Amanda Jamieson - Stress Management: Understanding Host Resilience to Infection Mark Johnson - Cell-cell communication essential for plant

reproduction

Thurs Oct 27 12:00

12:30

Tues Nov 1 12:00

12:30

Phyllis Dennery –

Richard Freiman – Regulating Meiosis, Gametogenesis and

Fertility.

Thurs Nov 3 12:00 12:30

Stephen Helfand - Molecular genetics of aging

Tues Nov 8 12:00 12:30

Thurs Nov 10 12:00 12:30

BIOM 2860: Molecular Mechanisms of Human Disease Contact … · 2019. 1. 23. · 1 BIOM 2860:...

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Transcript of BIOM 2860: Molecular Mechanisms of Human Disease Contact … · 2019. 1. 23. · 1 BIOM 2860:...