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

Transcription

1 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

2 a scientific utility

3 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

4 Raison d etre Mission: innovator of mouse models and molecular technologies that advance human and animal health Goals: 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.

5 Raison d etre Vision: to be a global leader in precision disease modeling to guide personalized medicine

6 Location, location, location Mouse Biology Program nd Street, Suite 400 Davis, California UCDMC (12 miles) City of Davis SFO (85 miles) University of California Davis

7 Reverse negotiation CryoTank Farm (Secondary) Resource/Research Laboratories Phenotyping Center CryoTank Farm (Primary) Restricted Vivarium* (*Barrier Vivarium off-site) Offices

8 People & diversity MBP Director Business Administration Phenotyping & Analytics Vivaria and Veterinary Care Laboratory Operations Information Services Phenotyping Center High- Containment MMCL Informatics MBML Restricted Access MSCL Repository Information Management People are our greatest asset diversity is our greatest strength : 131 employees (scientists, staff, and students) 63% female 46% under-represented minorities 5 persons with disabilities MTGL MGAL MCRL PI Concierge Services Import/Export Services Marketing & PR

9 People & diversity 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.

10 Customer empathy NIH funded activity Researcher needs

11 Customer empathy mice gene targeting FRT attl1 FRT loxp SA β gal neo pa ZeoR PheS attr1 attr2 attl2 loxp ES cells molecular constructs a/d/e pathology 5 arm 3 arm attr3 ori AmpR attr4 attl3 CmR ccdb attl4 ori KanR vectors PGK DTA pa microinjection adult phenotyping genotyping sperm & embryos embryo phenotyping expression analysis ips cells cryopreservation/ cryorecovery organs, tissues data, information sequence analysis rederivation/archiving

12 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

13 Public Service Number of Alleles All MMRRC Holdings UC Davis All Centers 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

14 Public Service Purchased from KOMP, MMRRC Procedures From PI CLAMS DEXA Gut Microbiome Created by MBP Phenotyping Core A Metabolism Endocrinology Mice for metabolic phenotyping Animal Care Core Phenotyping Core B Body Composition Thermoregulation Food Intake Phenotyping Services Phenotyping Core C Cardiovascular Biology Pathology

15 Public Service 7M + 7F Mutant Homozygous Adult Mice In life Terminal Open Field Grip strength Combined SHIRPA & Dysmorphology CTXII Urine Level Urinalysis 9 Hematology Clinical Blood Chemistry Weight Curve 4wk to 16wk scientists X-ray (5+5) Insulin Blood Level Auditory Brain Stem Gait Analysis Tail flick Response (4) Intraperitoneal Glucose Acoustic Startle/PPI Calorimetry Awake ECG products Tolerance Test & Body Composition services CTXII Blood Level Insulin Blood Level Fundoscopy Electroretinography Clinical Flow Cytometry Heart Weight institutions 16 Gross Pathology and Tissue Collection (2+2) Slit Lamp Tissue embedding & block banking (2+2) Histopathology (2+2) Mutant mice are subjected to a series of 30 phenotyping countries 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.

16 Managing up Comparative analysis of average project costs for MBP services incurred by 56 principal investigators at UC Davis during up to 90% savings using MBP

17 Outdo yourself every day Gene function Pluripotent stem cells CRISPR/Cas9 editing Laser-assisted IVF Gene expression analysis Metabolism of gastric bypass Compensatory transcriptomics

18 Outdo yourself every day 114 publications 194 grant applications $99,000,000 extramural research

19 Sustainability Space crunch Intellectual investment

20 The Vision thing vision

21 Technological evolution of (induced) mouse models Chemical mutagenesis Radiation Traditional approach: induced mutant mouse model informs relevant GH Transgenesis human phenotype ApoE Knockouts

22 Next-generation precision mouse models Disruptive approach: genetically-defined human phenotype informs relevant mouse model

23 Have fun. International Knockout Mouse Consortium International Mouse Phenotyping Consortium Federation of International Mouse Resources

24 Have fun. Largest NIH grant portfolio at UCD (top 0.3% in nation) ~230,000 vials germplasm ~2,320,000 mouse cages ~1,080,000 genotypes ~87,000 embryos for injection 1 st CRISPR flo x allele using 1 template ~11,600,000 mice (circles the earth!) ~500,000 ES cell clones ~58,000 tests (>2000 anesthesias) ~13,300 service tickets

25 Mouse Biology Program Your next mouse model is only a mouse click away