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IDENTIFICATION OF THE GENES REGULATED BY THE SIRT1 HISTONE DEACETYLASE AND THEIR CONTRIBUTION IN THE PATHOGENESIS OF TYPE 2 DIABETES AND OBESITY

Objective

Type 2 diabetes is the most common metabolic disease and is characterized by insulin resistance in the liver, adipose tissue and skeletal muscle and impaired insulin secretion. Type 2 diabetes is a polygenic disorder which also involves environmental factors and is tightly correlated with obesity. Therefore, the identification of the genes associated with increased susceptibility to these diseases is difficult. At present, therapies for this disease are not completely effective and present secondary effects. To design new therapies, a better knowledge of molecular regulation of the expression of genes implicated in the pathology of diabetes is necessary. Gene regulation at transcriptional level has been demonstrated to be directly correlated, among other factors, with chromatin structure which may be altered by covalent modifications of NH2-terminal end of histones, mainly through acetylation. The balance between acetyl transferase (HAT) and deacetylase (HDAC) activities controls the histone acetylation status. Among HDAC enzymes, sirtuin 1 (SIRT1) has been shown to suppress glycolytic pathway and to induce gluconeogenesis in the liver, two of the main alterations in the diabetic process. Thus, modifications in the histone acetylation level may be involved in the onset and the development of diabetes. Therefore, the main objective of this project is the identification of target genes for SIRT1 by using ChIP-chip methodology (hybridization of specific promoter microarrays (chip) with the products of chromatin immunoprecipitation (ChIP). The contribution of these genes to the diabetic process will be further evaluated by the generation and the study of genetically engineered animals by gene transfer. The results of this study may contribute to a better understanding of the mechanisms of gene transcription regulation, which may lead to potential development of new therapies for type 2 diabetes and obesity.

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Keywords

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2007-4-3-IRG
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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-IRG - International Re-integration Grants (IRG)

Coordinator

UNIVERSITAT AUTONOMA DE BARCELONA
EU contribution
€ 100 000,00
Address
EDIF A CAMPUS DE LA UAB BELLATERRA CERDANYOLA V
08193 Cerdanyola Del Valles
Spain

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Region
Este Cataluña Barcelona
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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