Disease Model Discovery

The aim of the Disease Model Discovery programme is to generate novel mouse models of disease providing a key resource for the elucidation and characterisation of new genes and pathways involved with diverse disease systems.

The programme delivers a critical underpinning to our intramural research programmes at MRC Harwell, as well as furnishing a wider platform for gene and pathway discovery for the biomedical sciences community within the UK and abroad.

Currently, large-scale mutagenesis and phenotyping platforms at MRC Harwell focus on the International Mouse Phenotyping Consortium (IMPC) pipeline for the generation and identification of mouse models.

The IMPC mutagenesis and phenotyping pipeline is a key ongoing programme for the discovery of novel genes associated with both early-onset and late-onset disease phenotypes. However, there is an increasing focus on the delivery of late-onset phenotypes. Diseases associated with ageing pose an increasing social and financial burden on society and represent a vital imperative for research in the biomedical sciences. There have been considerable advances, for example through GWAS studies, in identifying putative loci and pathways involved in diseases of ageing. Nevertheless, our knowledge of the genes and pathways involved with late-onset disease is neither comprehensive nor complete. As part of MRC funding to the Disease Model Discovery programme over the next five years we plan to introduce over 100 genes into the IMPC pipeline encompassing both early-onset and late-onset phenotyping platforms. This effort will be supplemented by additional funding from the NIH which will enable us to feed a further ~200 genes into the IMPC pipeline for the determination of both early and late-onset phenotypes. Proposals for genes to enter late-onset phenotyping will be sought via the regular calls to the UK community for gene nominations as part of the wider IMPC effort at MRC Harwell. In line with the wider IMPC programme, all data is freely available and deposited in the IMPC database – click here to find out more.

Overall, Disease Model Discovery at the Harwell Institute is at the forefront of delivering mutants, disease models and data that are a critical pillar for functional genomics studies across the biomedical sciences spectrum and provide key resources for understanding the genetic bases for disease and an important tool for the development of novel therapeutic strategies.