!!!WELCOME!!!

!!!WELCOME!!!

MRC MOUSE NETWORK

Launch Day

January 13th, 2012Harwell

Why Are We Here??

IMPC Engagement Strategy

BENEFITS OF SHARINGIndividual ResearchParadigm Shift in

Science

TOOL ACCESS DRIVES INNOVATION

HUMAN PROTEIN KINASES (518) (ordered by most citations 1950-2002)

CITA

TIO

NS

(nor

mal

ized

) 1950-2002

2003-2008

2009

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 = InnovationCorrelates 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 Score EVOLVING to Success

Key Team PlayersThey Will Deliver This Project

Production LacZ Profiling

Allele QCArchiving

Distribution Genotyping

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 Groups1. 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 (GLT) Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 TotalMRC 53 79 79 79 40 330NIH 40 50 50 50 0 190

Total 93 129 129 129 40 520

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

Production Centre"Assigned"

Genes%

Total IMPC (11 Production Centres)

2078 100%

UK Contribution (Harwell in Red)

1175 57%

(1) MRC 199 10%

(2) BaSH (All) 338 16%MRC 121 6%WTSI 72 3%

(BCM) 145 7%

(3) WTSI 783 38%

NOTE: Unclear GLT Rates (We assume 50%)

MMN SummaryConsortiumNumber of

Genes Assigned

In progress

ES cells to order

from Sanger

ES cells to order

from third party

Conflicts to resolve

Prioritize for

targeting

Overlapping Interest

(Consorita, Pis, Prod Centres)

Legacy/EUMODIC NA 40 0 0 0 0 0MGU PIs NA 22 0 0 0 0 2

Accelerated drug discovery 28 68 3 4 0 43 6Bone and cartilage disease 14 12 1 2 0 0 3Cardiovascular disease 14 9 3 2 0 0 0Development 14 13 2 0 0 0 1Diabetes and obesity 28 19 2 15 0 0 4Eye and vision disease 21 17 1 4 0 0 2Fibrosis and Tissue Remodelling 21 29 10 9 0 0 6Haematopoiesis and cancer 21 15 2 7 0 0 4Innate immunity 14 9 0 3 0 0 0Liver disease 21 19 4 3 0 0 2Neurodegenerative disease and aging

7 15 1 4 0 0 6

Neuromouse 28 21 5 14 0 3 4Renal disease 14 11 1 0 0 1 1Respiratory disease 14 11 2 4 0 0 4Adaptive Immunity 0 0 0 0 0 0 0

Host determinants to pneumoniae 0 0 0 0 0 0 0

Total Genes 259 330 37 71 0 47 45

HILARY HAS UPDATED TABLE AVAILABLE TODAY AS HARDCOPY

9

Mod

ified

SH

IRPA

/Dys

mor

phol

ogy

Ope

n Fi

eld

Grip

Str

engt

h

ECG

/ E

cho

Intr

aper

itone

al G

luco

se T

oler

ance

Tes

t

Audi

tory

Bra

in S

tem

Res

pons

e (2

+2)

Body

Com

posi

tion

(DEX

A)

X-ra

y (5

+ 5

)

Slit

Lam

p

Opt

halm

osco

pe

Hem

atol

ogy

Clin

ical

Blo

od C

hem

istr

y

Insu

lin B

lood

Lev

el

Gro

ss P

atho

logy

and

Tis

sue

Colle

ction

(2+

2)

Non-mandatory tests

Tis

sue

Embe

ddin

g an

d Bl

ock

Bank

ing

(2+2

)

Hea

rt W

eigh

tCa

lorim

etry

1310 11 14

16

15

7 M + 7 F Mutant Adult Mice

Chal

leng

e W

hole

Bod

y Pl

ethy

smog

raph

y

Acou

stic

Star

te/P

PI

12

In li

feTe

rmin

alWeight Curve – 4wk to 16wkWeight Curve – 4wk to 16wk

His

topa

thol

ogy

(2+2

) -

from

blo

cks

whe

re re

quire

d

Tests in development or under consideration

Mandatory tests

Final Adult Phenotyping Pipeline

FACS

ana

lysi

s –

bloo

d/sp

leen

?

Draft Pipeline – Under Consultation, Report Available(www.mousephenotype.org)

Dis

sect

ion

& g

ross

mor

phol

ogy

(em

bryo

s &

pla

cent

ae)

lacZ

sta

inin

g(e

mbr

yos

& p

lace

ntae

)

E12.5

≥7 Embryos from Sub-viable Lines

Adult Phenotyping Pipeline

IKMC mES cells (B6N)

Germline transmission

Heterozygotes

Homozygotes

Homozygotes

>40% expected homozygous mutants at weaningvi

able

subviable

<40% expected homozygousmutants at weaning

Dis

sect

ion

& g

ross

mor

phol

ogy

(em

bryo

s &

pla

cent

ae)

His

topa

thol

ogy

(em

bryo

s &

pla

cent

ae)

Em

bryo

μC

T(io

dine

sta

inin

g)

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 CriticalFIRST 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

Throughput1. Auditory Brainstem

Response2. Echo & ECG 3. Challenge Plethysmography

New Tests (eg NMR)

Existing Tests Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 TotalMRC 0 78 83 83 86 330NIH 30 40 50 50 20 190

Total 30 118 133 133 106 520

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 NetworkPromote 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

PublicPrivate ConsortiaPublicPrivate Consortia

PublicPrivate Consortia

MRC Mouse Network Community Portal (Andy Blake)

PublicPrivate Consortia

HarwellIMPC

mrcmousenetwork.har.mrc.ac.uk

CommunityNetworking

Group PostingIndividual MessagingForum for DiscussionProject 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

IMPC Specific Meeting

SOPs, Path,

LacZ??

Emb Lethal

IMPC/Infracomp General Meetings

MRC Mouse Network Timeline of Activity

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr MayMRC

Network Meetings

Launch MRC

Mouse Network

Network Meeting

Network Meeting

2012 2013

Planning & Reports

Finalize Program

of Activity

Consoria Interim Reports

MRC Expert Panel

Review

Revise Work PlansConsortia Project MeetingsConsortia Project Meetings

Access To Mice

Harwell & Other Production CentresAgree MRC MTA

Access To Data

EUMODIC Now, But DCC with Time.

Training

Custom Bioinfo (MMN Case

Studies)

Custom Bioinfo (MMN Case

Studies)

Option for operational training (eg IVF/Cryo, Phenotping).

Project Tracking

Portal iMits or Equivalent Tracking/Reports

Thank You!

www.mousephenotype.org