Transcript Slide 1

!!!WELCOME!!!
MRC MOUSE NETWORK
Launch Day
January 13th, 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)
CITATIONS (normalized)
Citations as a function of time,
Patent landscape equivalent
1950-2002
2003-2008
2009
Why the bottleneck in activity????
HUMAN PROTEIN KINASES (518)
(ordered by most citations 1950-2002)
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 Score
EVOLVING to Success
Key Team Players
They Will Deliver This Project
Martin F.
Production
Lydia T.
Deen Q.
Sara W.
Tertius H.
LacZ Profiling Cohort Breeding
Archiving
Distribution
Allele QC
Michael C.
Necropsy
Phenotyping
Genotyping
Mark G.
Quality Assurance
Pathology
Histology
Training
LIMS, Data Portal & Bioinformatics
Alison W.
Andy B.
Hugh M.
Finance, HR, Engagement
Liz M.
Hilary G.
Nanda R.
Annie M.
Project Management
MRC Working Groups
1.
2.
3.
4.
5.
6.
Work Plans & Reporting
Production (MF)
Allele QC & Genotyping (DQ/LT)
LacZ (LT)
Phenotyping (SW)
IT (AM)
Engagement (HG/NR)
 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)
Production (GLT) Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 Total
MRC 53 79 79 79 40 330
NIH 40 50 50 50 0 190
Total 93 129 129 129 40 520
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
"Assigned"
Genes
%
2078
100%
1175
57%
199
10%
(2) BaSH (All)
MRC
WTSI
(BCM)
338
121
72
145
16%
6%
3%
7%
(3) WTSI
783
38%
Production Centre
Total IMPC
(11 Production
Centres)
UK Contribution
(Harwell in Red)
(1) MRC
NOTE: Unclear GLT Rates
(We assume 50%)
ES cells ES cells
Prioritize
to order to order Conflicts
for
from
from third to resolve
targeting
Sanger
party
Overlapping
Interest
(Consorita,
Pis, Prod
Centres)
Number of
Genes
Assigned
In
progress
Legacy/EUMODIC
MGU PIs
NA
NA
40
22
0
0
0
0
0
0
0
0
0
2
Accelerated drug discovery
28
68
3
4
0
43
6
Bone and cartilage disease
Cardiovascular disease
Development
Diabetes and obesity
Eye and vision disease
Fibrosis and Tissue Remodelling
Haematopoiesis and cancer
Innate immunity
Liver disease
Neurodegenerative disease and
aging
Neuromouse
Renal disease
Respiratory disease
Adaptive Immunity
14
14
14
28
21
21
21
14
21
12
9
13
19
17
29
15
9
19
1
3
2
2
1
10
2
0
4
2
2
0
15
4
9
7
3
3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
3
0
1
4
2
6
4
0
2
7
15
1
4
0
0
6
28
14
14
0
21
11
11
0
5
1
2
0
14
0
4
0
0
0
0
0
3
1
0
0
4
1
4
0
Host determinants to pneumoniae
0
0
0
0
0
0
0
259
330
37
71
0
47
45
MMN Summary
Consortium
HILARY HAS UPDATED TABLE
AVAILABLE TODAY AS
HARDCOPY
Total Genes
16
Histopathology (2+2)
- from blocks where required
12
13
14
Opthalmoscope
Slit Lamp
X-ray (5 + 5)
Body Composition (DEXA)
Auditory Brain Stem Response (2+2)
Challenge Whole Body Plethysmography
Intraperitoneal Glucose Tolerance Test
Calorimetry
11
Tissue Embedding and Block Banking (2+2)
ECG / Echo
10
Heart Weight
Gross Pathology and Tissue Collection (2+2)
FACS analysis – blood/spleen?
Grip Strength
Modified SHIRPA/Dysmorphology
Open Field
In life
Acoustic Starte/PPI
9
Insulin Blood Level
Clinical Blood Chemistry
Hematology
Terminal
7 M + 7 F Mutant Adult Mice
Final Adult Phenotyping Pipeline
Weight Curve – 4wk to 16wk
15
Mandatory tests
Non-mandatory tests
Tests in
development or
under consideration
Proposed IMPC Embryonic
Phenotyping Pipeline
viable
>40% expected
homozygous
mutants at weaning
E12.5
(embryos & placentae)
Histopathology
Embryo μCT
(iodine staining)
viable
(embryos & placentae)
Homozygotes
Homozygotes
Dissection & gross morphology
<40% expected
homozygous
mutants at weaning
(embryos & placentae)
subviable
lacZ staining
Heterozygotes
(embryos & placentae)
Germline transmission
Dissection & gross morphology
≥7 Embryos from Sub-viable Lines
IKMC mES cells (B6N)
E14.5
Adult Phenotyping Pipeline
Draft Pipeline – Under Consultation, Report Available
(www.mousephenotype.org)
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)
Existing Tests
Yr 1 Yr 2 Yr 3 Yr 4 Yr 5 Total
MRC
0 78 83 83 86 330
NIH 30 40 50 50 20 190
Total 30 118 133 133 106 520
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.
2.
3.
Auditory Brainstem
Response
Echo & ECG
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)
MRC Mouse Network
Community Portal (Andy Blake)
Group Posting
Individual Messaging
Forum for Discussion
IMPC
Project Management
Private Consortia Public
Private Consortia Public
Private Consortia
Private Consortia
Harwell
IMPC
Public
Public
Community
Networking
mrcmousenetwork.har.mrc.ac.uk
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
Jan
Feb
Mar
Apr
May
Launch
MRC
MRC
Network
Mouse
Meetings Network
2012
Jun
Jul
Aug
Sep
Oct
Nov
Network
Meeting
Feb
Apr
May
IMPC/Infracomp General Meetings
MRC
Consoria
Expert
Interim
Revise Work Plans
Panel
Reports
Review
Consortia Project Meetings
Project
Portal
iMits or Equivalent Tracking/Reports
Tracking
Access To
Agree MRC MTA Harwell & Other Production Centres
Mice
Access To
EUMODIC Now, But DCC with Time.
Data
Training
Jan
Network
Meeting
IMPC
Specific
Meeting
SOPs,
Emb
Path,
Lethal
LacZ??
Finalize
Planning &
Program
Consortia Project Meetings
of
Reports
Activity
Dec
2013
Mar
Custom
Bioinfo
(MMN
Case
Studies)
Option for operational training (eg IVF/Cryo,
Phenotping).
Custom
Bioinfo
(MMN
Case
Studies)
Thank You!
www.mousephenotype.org