Objectif
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.
Champ scientifique
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesbasic medicinepathology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- medical and health scienceshealth sciencesnutritionobesity
Mots‑clés
Appel à propositions
FP7-PEOPLE-2007-4-3-IRG
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Régime de financement
MC-IRG - International Re-integration Grants (IRG)Coordinateur
08193 Cerdanyola Del Valles
Espagne