Late-onset systemic phenotyping (ageing pipeline)

INFRAFRONTIER2020 project - Trans-national Access call
(June 2017)

Context and aim of the call

INFRAFRONTIER is the European Research Infrastructure for phenotyping, archiving and distribution 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) (www.infrafrontier.eu).

INFRAFRONTIER2020 project and ageing

The INFRAFRONTIER2020 project aims to develop pilot platforms and services supporting ageing research. These activities are tightly integrated with the current efforts of the International Mouse Phenotyping Consortium (IMPC, www.mousephenotype.org) to set up a standardised late-onset (ageing) pipeline. In the IMPC phase 2 a significant fraction of mutant lines will be aged and re-phenotyped to identify genes involved with late-onset disease. The INFRAFRONTIER2020 Trans-national Access call complements the highly standardised IMPC late-onset phenotyping, as existing mouse lines with different mutations and genetic backgrounds can be tested with the IMPC late-onset phenotyping pipeline.

The INFRAFRONTIER open call facilitates access for the wider biomedical research community to the unique infrastructure and scientific expertise of the MRC Harwell mouse clinic. A total of four mouse mutant lines can be tested through a broad based late-onset phenotyping pipeline in all the major adult organ systems and most areas of major human disease and will be re-phenotyped at a later stage (weeks 52-59). Access to the service will be granted on the basis of scientific excellence and supports the development and in depth characterisation of mouse models for research on ageing and age-related diseases. INFRAFRONTIER will provide open access to all tested mouse lines and their phenotyping data.

Access modalities
  • The EC Horizon 2020 funded INFRAFRONTIER2020 project (2017 – 2020) supports eligible customers with a free of charge mouse late-onset phenotyping service implemented as a Trans-national Access activity providing a total of 4 access units.

  • The access unit offered covers the production of a cohort and a comprehensive first line phenotyping. The phenotyping will be performed at two different ages so that late onset of disease can be measured and / or the progression of disease with age.

  • Mutant mouse lines will be provided by the selected applicants either as breeding pairs or frozen embryos or sperm. MRC Harwell will breed the cohorts required for the pipelines, use the IMPC late-onset phenotyping pipeline and perform any relevant additional tests. Health status requirements to accept animals will be provided.

  • The phenotyping data will be made publicly available through a phenotyping database or as a phenotyping report. Successful applicants must submit phenotyped mouse mutant lines to the EMMA repository. An optional grace period of up to one year can be granted before data and mutant mouse lines must be released.

  • Costs: The access to the INFRAFRONTIER2020 phenotyping service is free of charge. However, the shipment cost of the starting material (breeding pairs or frozen embryos) to the MRC Harwell mouse clinic must be covered by the customers.

  • Eligibility: The INFRAFRONTIER2020 Trans-national Access call is open and proposals can be submitted from applicants around the world. Three projects must be allocated to applicants from EU Member States and Associated Countries, and one project can be allocated to applicants from third countries.

  • Application: Service requests for the INFRAFRONTIER2020 mouse phenotyping service can be made via this application form. Applications for the Trans-national Access activity must include a short description of the project involving the mouse mutant being phenotyped by the INFRAFRONTIER2020 TA service.

  • Selection procedure: Proposals from eligible customers for free of charge access to the INFRAFRONTIER2020 mouse phenotyping 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 phenotyped 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, relevance for ageing research and feasibility 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.

  • 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).
Support offered

MRC Harwell will provide Trans-national Access to researchers across Europe to submit mouse lines to their comprehensive phenotyping service. Four researchers will be able to use this Trans-national Access which builds upon the research performed in the EC-funded EUMODIC and INFRAFRONTIER-I3 projects. The centre is fully equipped with state of the art research instrumentation to facilitate comprehensive phenotypic analyses covering a wide range of physiological functions ranging from cardiovascular, neuro-behaviour and metabolism expertise to detailed pathology assessments. Routinely, all phenotyping activities are performed in a high-throughput fashion, as a service to support internal programs or for the wider scientific community.

MRC Harwell is a partner in the International Mouse Phenotyping Consortium (IMPC) and currently performs first-line phenotyping of around 140 lines per year.  This is funded by the UK MRC and the NIH.  Phenotyping is performed according to the standardised SOPs within an agreed pipeline of tests. The tests and pipeline for the late-onset phenotyping is currently being agreed by the IMPC. The proposed ageing pipeline is shown below. The INFRAFRONTIER2020 project opens up new areas to users, in that phenotyping will be performed at later ages allowing exploration of late-onset disease.  There are few laboratories equipped to offer this comprehensive phenotyping and access to it at later ages makes it a unique access. Users will benefit from access to the infrastructure and technical expertise of the MRC Harwell mouse clinic.  In addition, they will be given support by MRC Harwell to analyse and interpret the results. MRC Harwell will also suggest additional phenotyping tests that they can do to further describe the phenotypes.

Description of the phenotyping pipeline

In general, the provided 1st line phenotyping pipeline will be based on the IMPC pipeline for adult mutant mice as described at http://www.mousephenotype.org/. The standard pipeline may be adjusted during the course of the INFRAFRONTIER2020 project.

Late-onset phenotyping pipeline

IMPC late-onset phenotyping pipeline