IMPC into the future Funding runs until July 2016 (production finished by end of 2015) 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 technologies • 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 FEEDBACK from MMN Need more immediate delivery of lines and phenotyping data Need to serve current interests Need to increase the chances of delivery 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 gRNA 1 Cas 9 (D10A) Cas 9 (D10A) gRNA 2 Future Proposals ES cells from repository 100% ES cell Progress to a mixture of technologies for delivering mouse models CRISPR/Cas9 Embryonic injections • • Null alleles Complex alleles (in the future) CRISPR/Cas9 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?
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