!!!WELCOME!!! MRC MOUSE NETWORK Launch Day January 13 th, 2012 Harwell

Why Are We Here?? IMPC Engagement Strategy BENEFITS OF SHARING  Individual Research  Paradigm Shift in Science  TOOL ACCESS DRIVES INNOVATION

HUMAN PROTEIN KINASES (518) (ordered by most citations ) CITATIONS (normalized) Impact of Genome on Innovation (Al Edwards, SGX) Citations as a function of time, Patent landscape equivalent Why the bottleneck in activity???? Data kindly provided by Al Edwards)

Tool Access Key Nuclear Receptors (48 genes) “Druggable” so “Exciting” Data kindly provided by Al Edwards)

Research Activity = Innovation Correlates with tool access OUR GOAL IS TO EVEN OUT THIS DATA Data kindly provided by Al Edwards)

Meeting Objectives 1.Networking: Meet Consortia Champions Meet key people at Harwell working on the IMPC 2.Find out more about the IMPC & MRC Mouse Network Aims, timescale, status Tools to Assist Your Networks MMN Portal Training 3.Consoria Work Plans Presentation and discussion of tests proposed Other ways the Consortia are planning to contribute Clarifying the roles of Harwell and the Consortia

Expectations Route 1 to ScoreEVOLVING to Success

Key Team Players They Will Deliver This Project ProductionLacZ Profiling Allele QCArchiving DistributionGenotyping Cohort Breeding Phenotyping Histology Necropsy Finance, HR, Engagement LIMS, Data Portal & Bioinformatics Pathology Training Quality Assurance Martin F.Lydia T.Deen Q.Sara W.Tertius H.Michael C.Mark G. Alison W. Annie M. Liz M.Hilary G.Nanda R. Andy B. Hugh M.

Project Management MRC Working Groups 1.Production (MF) 2.Allele QC & Genotyping (DQ/LT) 3.LacZ (LT) 4.Phenotyping (SW) 5.IT (AM) 6.Engagement (HG/NR) Work Plans & Reporting  Targets  KPIs/Metrics  Organization  Resources  Critical Path Activity  Issue List Oversight  MRC IMPC Sr. Management Group  MRC External Advisory Group (Paul Luzio, Chair)  BaSH PI Group & Contribution to BaSH Working Groups

Production Plan (Martin Fray) Year 1 Major Efforts  Recruiting & cross skilling of existing staff  Candidate gene selection, ES cell access & QC  GLT Production: Scale up to 130 line/year minimum  Project Tracking: iMits tool in development  Tech Dev: Improved IVF, GLT

Production Status Candidate Gene Nomination, Assignment, Tracking  iMits Tool High Level Tracking of all 11 prod centres Logistical Challenge “Assignment” in IMPC  BaSH vs MRC vs Other Production Centres  To date 320 genes assigned to MRC (16% of total IMPC)  FLEXIBLE & “Exchange” between centres Access to ES cells  Sanger, HMGU, Davis

MMN Summary HILARY HAS UPDATED TABLE AVAILABLE TODAY AS HARDCOPY

9 Modified SHIRPA/Dysmorphology Open Field Grip StrengthECG / Echo Intraperitoneal Glucose Tolerance Test Auditory Brain Stem Response (2+2)Body Composition (DEXA)X-ray (5 + 5) Slit LampOpthalmoscope HematologyClinical Blood ChemistryInsulin Blood Level Gross Pathology and Tissue Collection (2+2) Non-mandatory tests Tissue Embedding and Block Banking (2+2) Heart Weight Calorimetry M + 7 F Mutant Adult Mice Challenge Whole Body Plethysmography Acoustic Starte/PPI 12 In life Terminal Weight Curve – 4wk to 16wk Histopathology (2+2) - from blocks where required Tests in development or under consideration Mandatory tests Final Adult Phenotyping Pipeline FACS analysis – blood/spleen?

Draft Pipeline – Under Consultation, Report Available ( Dissection & gross morphology (embryos & placentae) lacZ staining (embryos & placentae) E12.5 ≥7 Embryos from Sub-viable Lines Adult Phenotyping Pipeline IKMC mES cells (B6N) Germline transmission Heterozygotes Homozygotes >40% expected homozygous mutants at weaning viable subviable <40% expected homozygous mutants at weaning Dissection & gross morphology (embryos & placentae) Histopathology (embryos & placentae) Embryo μCT (iodine staining) E14.5 viable Proposed IMPC Embryonic Phenotyping Pipeline

IMPC & InfraComp Workshop on Embryonic Lethal Screening Two Day Workshop: April 18th-19th, 2012; Institute of Child Health, UCL  Organizers: Andy Copp (UCL), Janet Rossant (Univ Toronto), Tom Weaver (MRC Harwell), Tim Mohun (MRC NIMR), Monica Justice (Baylor), Michael Raess (HMGU) Goal: Agree a consensus strategy for embryonic phenotyping & LacZ analysis Topics:  Scientific Value of Embryology to Research Community  Current Status of Screening – Don’t reinvent the wheel, Funding opportunities  Operational Workflow – Not One Single Pipeline, Best Fits  LacZ Reporter Analysis – Agree Pipeline  Information Technology & Annotation Dev Consortia Input Critical FIRST MAJOR CONTRIBUTION FROM MRC MOUSE NETWORK

Phenotyping Plan (Sara Wells & Tertius Hough) Mouse Breeding Plan  Neo Cassette Deletion (TM1B, Magic Cre)  Cohort Expansion (bulk het x het)  Littermate Control Pilot Pipeline of Tests  Review SOPs/Parameter Sets  Refining the Basics  Pilot Tests to High Throughput 1.Auditory Brainstem Response 2.Echo & ECG 3.Challenge Plethysmography  New Tests (eg NMR)

Phenotyping Progress Recruiting & Reorg Complete All Equipment In place SOPs Almost Complete For Agreed Tests (MASSIVE TASK!) Tests in Development: Pilot Data Being Collected

Expectations For Network Promote IMPC and Mouse Models:  facilitate more road shows, participate in training course(s) Proactive Discussion/Planning:  Assign a “Champion” to be main contact with Harwell. Simplify, streamline the communication (gene lists, issues, ideas). Updated/Revised Plan in April.  Encourage the network to evolve so that individuals can work together rather than simple info flow from Harwell/Pis. Use the portal as a project management/coordination tool. Direct Participation: Actions with Added Value to Program  Pilot Work: Kick-start secondary phenotyping  Active Uptake of Lines/Data Feedback:  We will ask for a report at end of first year (spring 2013), will influence development of the program

On-line Portal Individual members of the MRC Mouse Network will be able to communicate directly to one another in a manner similar to “Facebook” mrcmousenetwork.har.mrc.ac.uk Site Launched Today (replace current portal)

IMPC Public Private Consortia Public Private Consortia Public Private Consortia MRC Mouse Network Community Portal (Andy Blake) Public Private Consortia Harwell IMPC mrcmousenetwork.har.mrc.ac.uk Community Networking Group Posting Individual Messaging Forum for Discussion Project Management

Key Functionalities Important Functions  Secure Log in (already registered!)  General Information  News  Events  Forum => Incredibly Useful for IMPC Nov 2008, 156 Active Users, 24 Forums, 300 Forum Threads, 8K page views….  My Consortium  All Consortia Demos (WebEx) Will Be Arranged Soon

Training For Networks The Network will promote training in the form of workshops, training courses, and site visits.  Mouse Genome Browsing, Mutant Mouse Resources  Customize to MMN  Develop Case Studies, eg GWAS => Candidates => Resources Available  May 2012

MRC Mouse Network Timeline of Activity

Thank You!