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Content archived on 2024-06-18

Genetical genomics of type 2 diabetes and cardiovascular phenotypes in experimental systems

Objective

The objectives of this proposal are to establish causal relationships between altered gene expression regulation and diabetes metabolic changes in a rat model of spontaneous insulin resistance, the Goto-Kakizaki (GK) strain, and define disease-associated biomarkers. This multidisciplinary research addresses fundamental questions concerning the impact of naturally-occurring genetic variants on metabolic regulations contributing to diabetes and obesity, which have become dominant causes of reduced life expectancy in westernized societies. The proposed research builds on knowledge of genetic loci linked to variables relevant to insulin resistance and quantitative changes in metabolites derived by metabonomics, as well as advances in functional genomic technologies and expanding rat genomic resources (genome sequence, single nucleotide polymorphism - SNP). This research takes advantage of the availability of congenic strains of the GK rat, which are powerful tools for validating results from genetic and genetical genomic experiments and testing hypotheses regarding the involvement of SNPs in disease features. In this programme gene transcription profiling, bioinformatic tools and metabolic and biochemical studies will be applied in existing congenic strains of the GK rat carrying chromosomal regions of a locus associated with insulin resistance, transferred onto the genetic background of a control strain. Gene pathways and networks associated with altered metabolic variables will be correlated with SNP-derived haplotypes of the parental strains across the congenic intervals in order to fine map the causative genetic variant(s). This strategy, which integrates different mechanistic levels of gene expression (transcriptome and metabonome), will define biomarkers associated with or predicting disease onset and progression and provide key information for identifying the underlying genes. Results will provide improved knowledge for therapeutic targets and disease prevention.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Topic(s)

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Call for proposal

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FP7-PEOPLE-2007-2-1-IEF
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
EU contribution
€ 178 307,05
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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