Future operations - Sara Wells

IMPC into the future
Funding runs until
July 2016 (production
finished by end of
International consortia currently
putting together a business plan
Preparing an
application for
refunding to MRC
Strategy Board
Future Proposals- phenotyping
Requirements for the future:
• Accurate data
• More Data
• Cost effective
• Includes Development
Refine and refresh:
• Analysis of 1700+
• Value-judgements
• New automated
• Maintain and develop
husbandry information
Changes to the Operating Model at Harwell
Original gene-list was a long-ranging
Although dynamic, delivery of lines
could be anytime in years 1-4
Need more immediate delivery of lines
and phenotyping data
Need to serve current interests
Need to increase the chances of
Genome Coverage
ES cell repositories only cover 15,000 genes
QC issues with a significant proportion of these
GLT is only 50%
Some gene refractory to classic targeting approaches
Requirements for the future:
• Quicker delivery
• Increased likelihood of delivery
• Be able to include genes which are not-targeted or ES-cell
clones have not passed QC
Cas 9 (D10A)
Cas 9 (D10A)
Future Proposals
ES cells from repository
ES cell
Progress to a mixture of
technologies for delivering
mouse models
Embryonic injections
Null alleles
Complex alleles (in the future)
ES cell manipulation
• Complex alleles
We proposed to use CRISPR technology to make 50 of the lines left
for this phase (null alleles).
50 lines for Phase I
Role of MMN in gene nomination?
• Call throughout the existing networks to
apply for these null alleles to be produced
• If over subscribed, genes prioritised by a
transparent scoring method
• Criteria to include:
 Genes where there is no known model
 No ES cell clones (or of poor quality)
 Imminent need for model or phenotyping data
Future of MMN and IMPC
50 CRISPR lines- A pilot for the future?
MRC Mouse Networks
• Increase the number of laboratories involved?
• Support for more consortia meetings?
• Provide a forum for discussion
• Communications network for calls for gene nomination
• A forum for developments in primary phenotyping
• Delivering secondary phenotyping to the DCC?