Model development and systemic phenotyping call - December 2016

Main objective of the INFRAFRONTIER open call is to facilitate access for the wider biomedical research community to the unique infrastructure and scientific expertise of the participating mouse clinics. Mouse mutant lines can be tested through a broad based primary phenotyping pipeline in all the major adult organ systems and most areas of major human disease. Access will be granted on the basis of scientific excellence and supports the development and in depth characterisation of new mouse models for investigating gene function and human pathophysiology. INFRAFRONTIER will provide open access to all newly developed disease models and phenotyping data.

Scope and modalities

  • Applications for the INFRAFRONTIER call can be submitted from scientists across the world. Access will be granted based on scientific excellence and no regional restrictions will apply
  • A total of 15 model development and phenotyping projects will be supported. Access is provided free of charge and on a collaborative basis. The only costs to be borne by the applicants are shipment cost of materials to and from the mouse clinics
  • Participating mouse clinics are Phenomin-ICS, the Czech Centre for Phenogenomics (CCP), and the German Mouse Clinic (GMC)
  • Mouse models can be developed using either genome editing approaches (C57BL/6N genetic background only) or by injecting targeted ES cells of the IKMC resource. Only new mouse models will be developed that are not yet in the production pipelines of the International Mouse Phenotyping Consortium (IMPC, https://www.mousephenotype.org/imits). Alternatively, starting materials can also be a breeding nucleus or cohorts ready for phenotyping (acceptance depending on health certificates). In the latter case mouse mutants from various sources (transgenes, knockout mice, mutants from mutagenesis screens like ENU) and of different genetic backgrounds can be accepted
  • The phenotyping pipelines to be used will be either broad based primary phenotyping pipelines with a possible customisation or the adult IMPC phenotype pipeline (http://www.mousephenotype.org/impress)
  • Support will be provided by the mouse clinics to analyse and interpret the phenotype data
  • A final report with all phenotype data will be prepared, and data will also be uploaded onto a public phenotype database of the mouse clinics and / or onto the IMPC portal
  • The generated mouse resources and phenotype data will be made available to the whole scientific community. An optional grace period of up to 1 year for mouse resources and phenotype data may apply, with immediate release of mouse resources and data after expiry of the grace period. Mouse mutant lines will be deposited into the INFRAFRONTIER/EMMA repository for subsequent use by the scientific community
Proposal submission

Service requests for the INFRAFRONTIER Research Infrastructure call can be made via this application form. Call applications must be accompanied by a short description of the project involving the mouse mutant being developed and phenotyped by the INFRAFRONTIER mouse clinics

Deadline for submission of propsoals: 15 February 2017

Informal enquiries prior to proposal submission are welcome via proposals@infrafrontier.eu

The evaluation process is scheduled for the period from 16 February to 31 March 2017

Generation of mouse models

Mouse models can be generated by Phenomin-ICS and CCP using different approaches:

1) From ES cells of the IKMC / IMPC resource
New models will only be generated if production is not yet assigned to the pipelines of IMPC partners. ES cell derived models will be generated on a C57BL/6N genetic background. In a first step knock-out models with conditional potential (knock-out first allele, tm1a) will be produced from which tm1b null alleles can be derived for phenotyping

ES cells must be sourced by applicants from ES cell repositories and projects will only be initiated if two independent quality controlled ES cell clones are available

2) If ES cell clones are not available from the IKMC / IMPC resource, mouse models will be generated using genome editing approaches such as CRISPR/Cas9 nuclease technology (on C57BL/6N genetic background only) and may cover constitutive knock-outs or point mutations. Conditional mouse models using genome editing approaches cannot be generated within the frame of this call

Expansion and phenotyping

Newly developed mouse lines will be expanded for the first line phenotyping. In general, the phenotyping pipeline will be based on the IMPC pipeline for adult mutant mice as described at http://www.mousephenotype.org/

Pipeline summary

Access to mouse models and data for applicants and the scientific community

Newly developed mouse models will be made available to selected applicants within an average of twelve months following provision of all required information and materials to start the mouse production. To facilitate access by the wider scientific community, mouse lines will be cryopreserved and distributed by the INFRAFRONTIER/EMMA repository. Newly developed mouse models will be owned by the selected applicants and will be distributed by the INFRAFRONTIER/EMMA repository using their institutional MTAs

If a mouse mutant line was provided by selected applicants for a phenotyping project, sharing of the mouse line is also required and facilitated by the INFRAFRONTIER/EMMA repository. Archiving and distribution will follow standard conditions of the EMMA repository

For newly developed mouse mutant lines and phenotyping based on the IMPC pipeline, phenotype data will be made publicly available with no delay on the IMPC portal. When a cohort was provided for phenotyping, resulting phenotype data will be available to applicants within 9 months. For customized phenotyping pipelines a grace period of up to 1 year may apply. Following expiry of an optional grace period, phenotype data will ultimately be made publicly available through a phenotyping database

Evaluation of proposed projects

Project proposals will be subject to a competitive review procedure which will be initiated after calls for applications are closed. The review will be based on short descriptions of the projects involving the mouse mutants that will be developed and phenotyped by the INFRAFRONTIER mouse clinics. A mixed panel consisting of members of the INFRAFRONTIER Research Infrastructure and of the external INFRAFRONTIER Evaluation Committee will assess project proposal

1) Scientific evaluation and evaluation criteria

The scientific aspects of project proposals will be evaluated by an expert panel that is independent of the INFRAFRONTIER Research Infrastructure. Main criteria considered for project evaluation are:

  • Scientific merit of applicant
  • Experience of applicant in mouse model exploration
  • Relevance and quality of preliminary data
  • Relevance of animal model for human disease
  • Project objectives and prospects for exploitation of phenotype data
2) Technical feasibility

In a further step the technical feasibility and eligibility of projects will be assessed by experts of the mouse clinics. The technical evaluation of projects may require the provision of additional data such as information on the genetic modification of your mutant mouse line if applicable (e.g. affected gene, MGI ID of the gene, type of mutation, ES-cell line used, genetic background (e.g. number of backcross generations), safety level, description of DNA modification, vector, remaining non-recipient DNA, donor organism), mutant phenotype(s), special housing or care requirements, current sanitary status, and intellectual property rights (who generated the mouse line, owner of the mouse line)

Informal enquiries prior to proposal submission are welcome via proposals@infrafrontier.eu

Selected projects

Centre specific collaboration agreements will be established between applicants and the mouse clinics. Selected projects will be allocated to the mouse clinics based on scope of submitted project proposals

Funding

The access to the INFRAFRONTIER mouse clinics is free of charge and on a collaborative basis. However, all shipment cost of ES cells or mice to and from the mouse clinics must be covered by the applicants. In the case of the German Mouse Clinic a breeding nucleus or a cohort for phenotyping must be provided by the applicants

Participating INFRAFRONTIER mouse clinics

Czech Centre for Phenogenomics (CCP)

The Czech Centre for Phenogenomics provides expertise and services to the biomedical research community which study the function of genes in biological processes and / or human disorders in vivo using mouse or rat models. CCP covers a full spectrum of genetic engineering services, strain cryopreservation and archiving services, advanced phenotyping and imaging services, as well as specific pathogen free (SPF) animal housing and husbandry.

German Mouse Clinic (GMC)

The German Mouse Clinic was founded 2001 at the Helmholtz Zentrum München as the first mouse clinic with open access

Goal: Characterisation of mouse models for human diseases to understand molecular mechanisms of human disorders and for the development of new therapies

GMC strategy: To develop and offer a large scale standardised and comprehensive phenotypic analysis of mouse mutants from various sources (e.g. transgenic lines, knockout mice, ENU mutants or endonuclease mediated mutations)

Phenotype your mouse mutants: We offer the examination of mouse mutants using a broad standardised phenotypic check-up with more than 550 parameters. The screens in the German Mouse Clinic are designated to the areas of behaviour, bone and cartilage development, neurology, clinical chemistry, eye development, immunology, allergy, steroid metabolism, energy metabolism, lung function, vision and pain perception, molecular phenotyping, cardiovascular analyses and pathology

Phenomin-ICS

PHENOMIN is founded by 3 major national nodes: the Institut Clinique de la Souris (ICS, Illkirch), the Transgenesis and Archiving of Animal Models (TAAM, Orléans, Villejuif) and the Centre for Immunophenomics (CIPHE, Marseille) that are devoted to serve the scientific community for the usage of mouse models. PHENOMIN constitutes a unique distributed resource for the creation, the care, the phenotyping, the distribution and archiving of animal models for academics and private corporations.

The ICS is a large-scale facility open to the community that ensures the generation of mouse models à la carte, the validation of genetic models, the expansion and preservation and distribution of models with the housing department, and offers in its phenotyping department a series of standardized functional analysis of mouse models that can be performed in a comprehensive pipeline or on demand, as well as for more specialized studies, that cover the major functions and key physiological systems.