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!!!WELCOME!!!

!!!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. Impact of Genome on Innovation (Al Edwards, SGX).

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!!!WELCOME!!!

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  1. !!!WELCOME!!! MRC MOUSE NETWORKLaunch DayJanuary 13th, 2012Harwell

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

  3. Impact of Genome on Innovation(Al Edwards, SGX) Citations as a function of time, Patent landscape equivalent 1950-2002 2003-2008 CITATIONS (normalized) 2009 Why the bottleneck in activity???? Data kindly provided by Al Edwards) HUMAN PROTEIN KINASES (518) (ordered by most citations 1950-2002)

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

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

  6. Meeting Objectives • Networking: • Meet Consortia Champions • Meet key people at Harwell working on the IMPC • Find out more about the IMPC & MRC Mouse Network • Aims, timescale, status • Tools to Assist Your Networks • MMN Portal • Training • 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

  7. Expectations Route 1 to Score EVOLVING to Success

  8. Key Team PlayersThey Will Deliver This Project Martin F. Lydia T. Deen Q. Sara W. Tertius H. Michael C. Mark G. Production LacZ Profiling Cohort Breeding Necropsy Quality Assurance Archiving Allele QC Phenotyping Pathology Distribution Genotyping Histology Training LIMS, Data Portal & Bioinformatics Andy B. Alison W. Hugh M. Annie M. Finance, HR, Engagement Liz M. Hilary G. Nanda R.

  9. Project Management MRC Working Groups • Production (MF) • Allele QC & Genotyping (DQ/LT) • LacZ (LT) • Phenotyping (SW) • IT (AM) • 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

  10. 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

  11. Production Status • Candidate Gene Nomination, Assignment, Tracking • iMits Tool High Level Tracking of all 11 prod centres • Logistical Challenge • “Assignment” in IMPC • BaSHvs 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

  12. MMN Summary HILARY HAS UPDATED TABLE AVAILABLE TODAY AS HARDCOPY

  13. Final Adult Phenotyping Pipeline 7 M + 7 F Mutant Adult Mice Weight Curve – 4wk to 16wk In life Challenge Whole Body Plethysmography Intraperitoneal Glucose Tolerance Test Modified SHIRPA/Dysmorphology Auditory Brain Stem Response (2+2) Body Composition (DEXA) Acoustic Starte/PPI Open Field Opthalmoscope Grip Strength X-ray (5 + 5) Calorimetry ECG / Echo Slit Lamp 9 10 11 13 15 12 14 Mandatory tests Non-mandatory tests Tests in development or under consideration Gross Pathology and Tissue Collection (2+2) Tissue Embedding and Block Banking (2+2) Terminal Histopathology (2+2) - from blocks where required FACS analysis – blood/spleen? Clinical Blood Chemistry Insulin Blood Level Heart Weight Hematology 16

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

  15. 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

  16. 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 • Auditory Brainstem Response • Echo & ECG • Challenge Plethysmography • New Tests (eg NMR)

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

  18. 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

  19. 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)

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

  21. 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

  22. 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

  23. MRC Mouse Network Timeline of Activity

  24. Thank You! www.mousephenotype.org

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