The UC Davis Mouse Biology Program: a test case in...

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The UC Davis Mouse Biology Program: a test case in core sustainability”

GENERAL INTEREST SESSION 2: OPS MANAGEMENT: DOLLARS AND SENSE

Western Association of Core Directors UC DAVIS CONFERENCE CENTER THURSDAY, 11 SEPTEMBER 2014

…a “scientific utility”

Sustainability factors: Raison d’etre Strong foundation, rationale Location, location, location “Reverse negotiation” People are asset…diversity is strength Customer empathy Public Service Managing “up” Outdo yourself…every day The vision thing Have fun

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Pursue reproducible research and discovery using mutant mouse models

Promote training and mentoring in mutant mouse science & technologies

Provide next-generation mouse biology services and resources.

…innovator of mouse models and molecular technologies that advance human and animal health…

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Raison d’etre

Mission:

Goals:

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

…to be a global leader in precision disease modeling to guide personalized medicine

Vision:

Raison d’etre

City of Davis

University of California Davis

SFO (85 miles)

UCDMC (12 miles)

Location, location, location

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Mouse Biology Program 2795 2nd Street, Suite 400

Davis, California

Phenotyping Center CryoTank Farm (Primary)

CryoTank Farm (Secondary)

Restricted Vivarium*

Resource/Research Laboratories

Offices (*Barrier Vivarium off-site)

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

“Reverse negotiation”

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

MBP Director

Phenotyping & Analytics

Phenotyping Center

MBML

Vivaria and Veterinary Care

High-Containment

Restricted Access

Laboratory Operations

MMCL

MSCL

MTGL

MGAL

MCRL

Information Services

Informatics

Repository Information

Management

PI Concierge Services

Import/Export Services

Marketing & PR

Business Administration

People are our greatest asset… …diversity is our greatest strength

2013-2014: 131 employees (scientists, staff, and students) 63% female 46% under-represented minorities 5 persons with disabilities

People & diversity

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Town Hall Meeting: May 13, 2014

MBP Staff Survey

MBP Retreat: May 30, 2014

Town Hall Follow-up Meeting: July 15, 2014

Some outcomes so far… Re-issue of MBP Quarterly Newsletter Regular Town Hall/All Hands Meetings Laboratory Intercommunications Meetings Employee Recognition Programs Strategic Planning Exercise and more….

People & diversity

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

NIH funded activity Researcher needs Customer empathy

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

microinjection

cryopreservation/ cryorecovery

genotyping

molecular constructs a/d/e pathology

adult phenotyping

embryo phenotyping expression analysis

sequence analysis

gene targeting

rederivation/archiving

mice

sperm & embryos

ES cells

vectors

attR1

ZeoR PheS

attR2 loxP

AmpR ori

attR3 attR4

5 ’ arm 3 ’ arm

attL2 attL1 FRT

β gal neo pA

FRT

SA

loxP

attL4 attL3 CmR ccdB

ori

PGK DTA pA

KanR

attR1

ZeoR PheS

attR2 loxP

AmpR ori

attR3 attR4

5 ’ arm 3 ’ arm

attL2 attL1 FRT

β gal neo pA

FRT

SA

loxP

attL4 attL3 CmR ccdB

ori

PGK DTA pA

KanR

attR1

ZeoR PheS

attR2 loxP

AmpR ori

attR3 attR4

AmpR ori

attR3 attR4

5 ’ arm 3 ’ arm

attL2 attL1 FRT

β gal neo pA

FRT

SA

loxP attL2 attL1 FRT

β gal neo pA

FRT

SA

loxP

attL4 attL3 CmR ccdB

ori

PGK DTA pA

KanR

attL4 attL3 CmR ccdB

ori

PGK DTA pA

KanR

iPS cells

organs, tissues data, information

Customer empathy

Students (>90): Undergraduate students Graduate students Post-doctoral fellows Professional students (VetMed, Med) Clinical Residents (LAM, Path) “HELP” Program

Lectures: ETX 250 Reproductive Toxicology IMM 293 Immunological Concepts MCRTP Summer Methods Course MMI 210 Animals Models in Infectious Diseases PHR408 Mouse Models in Research PMI 280A Experimental Mouse Biology VMB 253 Toxicant and Drug Metabolism ETC 278 Forensic Science

Courses: EMMA Cryopreservation Courses Center for Genomic Pathology

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Customer empathy

0

5000

10000

15000

20000

25000

30000

35000

All MMRRC Holdings

UC Davis

All Centers

Num

ber o

f Alle

les

MMRRC Mice & Germplasm Total number = 3880

MMRRC Repository Locations University of North Carolina UC Davis (also ICSC/Data Center) The Jackson Laboratory University Missouri-Columbia

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Public Service

Phenotyping Core A

• Metabolism • Endocrinology

Phenotyping Core B

• Body Composition • Thermoregulation • Food Intake

Phenotyping Core C

• Cardiovascular Biology • Pathology

Animal Care Core

Mice for metabolic phenotyping

Created by MBP

Purchased from KOMP,

MMRRC From PI

Phenotyping Services

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Procedures CLAMS DEXA

Gut Microbiome

Public Service

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

7M + 7F Mutant Homozygous Adult Mice

Weight Curve – 4wk to 16wk

9

Combined SHIRPA & Dysmorphology

Grip strength

Open Field

Acoustic Startle/PPI

10

Calorimetry

11

Awake ECG Intraperitoneal Glucose Tolerance Test

Auditory Brain Stem Response (4)

X-ray (5+5)

Body Composition

Fundoscopy

Electroretinography

12 13 14 15

In li

fe

16

Hematology Clinical Blood Chemistry

Insulin Blood Level

Clinical Flow Cytometry Heart Weight

Gross Pathology and Tissue Collection (2+2)

Histopathology (2+2) Urinalysis Te

rmin

al

Slit Lamp Insulin Blood Level Gait Analysis Tail flick

CTXII Blood Level CTXII Urine

Level

Tissue embedding & block banking (2+2)

Mutant mice are subjected to a series of phenotyping screens that are sequentially arranged to minimize interference on subsequent assays. Tests have been selected to assess a broad range of clinically-relevant physiological and behavioral systems.

2500+ scientists

9000+ products & services

2000+ institutions

30 countries

Public Service

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Comparative analysis of average project costs for MBP services incurred by 56 principal investigators at UC Davis during 2009-2010

up to 90% savings using MBP

Managing “up”

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Gene expression analysis

Pluripotent stem cells Laser-assisted IVF

Compensatory transcriptomics

Gene function

Metabolism of gastric bypass

CRISPR/Cas9 editing Outdo yourself…every day

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

114 publications

194 grant applications

$99,000,000 extramural research

Outdo yourself…every day

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Space crunch

Sustainability

Intellectual investment

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

vision

The Vision thing

Technological evolution of (induced) mouse models

Chemical mutagenesis Radiation

Transgenesis

GH

Knockouts

ApoE

Traditional approach: induced mutant mouse model informs relevant human phenotype

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Next-generation “precision” mouse models

Disruptive approach: genetically-defined human phenotype informs relevant mouse model

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

International Knockout Mouse Consortium International Mouse Phenotyping Consortium Federation of International Mouse Resources

Have fun.

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

~500,000 ES cell clones

~58,000 tests (>2000 anesthesias)

~87,000 embryos for injection

~1,080,000 genotypes

1st CRISPR flo’x allele using 1 template

~230,000 vials germplasm

~2,320,000 mouse cages

~13,300 service “tickets”

~11,600,000 mice (circles the earth!)

Largest NIH grant portfolio at UCD (top 0.3% in nation)

Have fun.

Your next mouse model is only a mouse click away…

www.mousebiology.org mbp@ucdavis.edu @mousebiology 2795 2nd Street Suite 400 Davis, CA 95616 (530) 754-MOUSE

Mouse Biology

Program www.mousebiology.org