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

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

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



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…

Raison d’etre

Mission:

…to be a global leader in precision disease modeling

to guide personalized medicine

Vision:

City of Davis

University of California

Davis

SFO (85 miles)

UCDMC

(12 miles)

Location, location, location

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)

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

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….

NIH funded activity

Researcher needs

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

iPS cells

organs, tissues

data, information

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

0 5000 10000 15000 20000 25000 30000 35000

All MMRRC Holdings

UC Davis

All Centers

Nu

m

be

r o

f Alle

le

s

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

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

Procedures

CLAMS

DEXA

Gut Microbiome

Public Service

7M + 7F Mutant Homozygous Adult Mice

Weight Curve – 4wk to 16wk

9

10

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

lif

e

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

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

Gene expression analysis

Pluripotent stem cells

Laser-assisted IVF

Compensatory transcriptomics

Gene function

Metabolism of gastric bypass

CRISPR/Cas9 editing

114 publications

194 grant applications

$99,000,000 extramural research

Space crunch

Sustainability

Intellectual

investment

vision

Technological evolution of (induced) mouse models

Chemical mutagenesis

Radiation

Transgenesis

GH

Knockouts

ApoE

Traditional approach:

induced mutant mouse model informs relevant

human phenotype

Next-generation “precision” mouse models

Disruptive approach:

genetically-defined human phenotype informs

relevant mouse model



International Knockout Mouse Consortium



International Mouse Phenotyping Consortium



Federation of International Mouse Resources

~500,000 ES cell clones

~58,000 tests (>2000 anesthesias)

~87,000 embryos for injection

~1,080,000 genotypes

1

st

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)

Your next mouse model is

only a mouse click away…

Mouse Biology

Program

www.mousebiology.org