Precision mammalian model development
INFRAFRONTIER2020 project - Trans-national Access call
Context and aims of the call
INFRAFRONTIER is the European Research Infrastructure for phenotyping and archiving of model mammalian genomes. The INFRAFRONTIER Research Infrastructure provides access to first-class tools and data for biomedical research, and thereby contributes to improving the understanding of gene function in human health and disease using the mouse model. The core services of INFRAFRONTIER comprise the systemic phenotyping of mouse mutants in the participating mouse clinics, and the archiving and distribution of mouse mutant lines by the European Mouse Mutant Archive (EMMA).
Main objective of this INFRAFRONTIER open call is to facilitate access for the wider biomedical research community to the unique infrastructure and scientific expertise of the participating INFRAFRONTIER partners, to deliver novel mouse lines that will advance knowledge of human disease and will be of widespread use in biomedical science. Recent advances in genome editing technology will be used to develop new mouse models of human disease. INFRAFRONTIER will provide open access to all newly developed disease models through the European Mouse Mutant Archive (EMMA). Access to this free-of-charge-service will be granted on the basis of the applicant's research plans and the potential impact of the proposed novel mouse line on the wider biomedical research community.
During the course of the INFRAFRONTIER2020 project a total of 3 Trans-national Access calls for the development of mammalian model development supporting a total of 28 projects will be published. Further calls supporting 10 mouse model and 6 rat model development projects will be released in 2018.
- The EC Horizon 2020 funded INFRAFRONTIER2020 project (2017 – 2020) supports eligible customers with a free-of-charge mouse model development service implemented as a Trans-national Access activity supporting a total of 12 projects in this first call
- The access unit offered covers the production of a single F1 genome-edited mouse line (at least one individual of a F1 genome edited mouse line will be provided)
- The model development service involves project design including prediction of off-target sites, preparation of sgRNA’s and Cas9 mRNA/protein, and injection into zygotes to generate F0 founder mutant animals (C57BL/6N or C57BL/6J genetic background preferred). Selected F0 animals will be bred to germ line to produce F1 genome edited animals. Possible allele types that can be generated are indels, exon deletions (< 10kb) and point mutation insertions. Newly developed mouse models will be made available to selected applicants within an average of 12 months following provision of all required information to start the mouse production
- The generated mouse models will be made available to the scientific community. An optional grace period of up to 1 year for mouse resources may apply, with immediate release of mouse resources after expiry of the grace period. Mouse mutant lines will be deposited into the INFRAFRONTIER/EMMA repository for subsequent use by the scientific community. Newly developed mouse models will be owned by the production centres and will be distributed by the INFRAFRONTIER/EMMA repository using their institutional MTAs
- Costs: The access to the INFRAFRONTIER2020 model development service is free of charge. However, the shipment cost of the newly developed mouse models must be borne by the applicants
- Eligibility: The INFRAFRONTIER2020 Trans-national Access call is open and proposals can be submitted from applicants around the world. Ten projects must be allocated to applicants from EU Member States and Associated Countries, and two projects can be allocated to applicants from third countries
- Application: Service requests for the INFRAFRONTIER2020 model development service can be made via this application form. Applications for the Trans-national Access activity must include a short description of the research plans for utilising the newly developed mouse model that is being generated by the INFRAFRONTIER2020 TA service
- Selection procedure: Proposals from eligible customers for free of charge access to the INFRAFRONTIER2020 mouse model development service will be subject to a review procedure. The review will be based on short descriptions of the projects involving the mouse mutants that will be produced by the TA service. A mixed panel of members of INFRAFRONTIER and of an external Evaluation Committee will assess service requests supported by the TA activity. In addition to scientific merit of applicants, soundness of the proposal and research plans, and the beneficial impact of the proposed novel mouse line on the wider biomedical research community will be assessed. Applicants will be informed on the outcome of the evaluation within 6 weeks after the end of the call for which the TA application was submitted. All applications will be handled with strict confidentiality.
- Acknowledgements: Please do acknowledge any support under this scheme in all resulting publications with "Part of this work has been funded by the European Union Research and Innovation programme Horizon 2020 (Grant Agreement Number 730879). The participating infrastructure which provided the service should be specifically mentioned in any publication resulting from the service.
Beyond the TA service provision applicants will benefit from extensive user support which covers detailed consulting on project design. Gene-editing approaches frequently yield a number of mutant alleles which can be provided and cryopreserved (at additional cost) for later use as only selected founder animals will be bred to the F1 generation. Logistic support will be provided by arranging shipments to the applicant's animal facilities. At additional cost a colony expansion can be provided. For long term availability new animal models will be cryopreserved by the participating production centres at own cost and deposited into the EMMA repository.
The participating INFRAFRONTIER partners routinely provide mouse model development services using all standard approaches such as gene targeting, the generation of chimeric mice from gene-targeted ES cells and gene editing technologies such as TALENs or CRISPR/Cas9. Participating centres like the Sanger Institute are engaged in large scale in house production projects and have a capacity of 100 to 150 model development projects per year. Partners operating transgenic service platforms routinely provide model development services to academic clients from across the world.
- Biological Sciences Research Centre A. Fleming (Fleming)
- Agencia Estatal Consejo Superior de Investigaciones Cientificas (CSIC-CNB)
- Netherlands Cancer Institute (NKI)
- Genome Research Limited (Sanger Institute)