Research objectives and content
The transcription factor Peroxisome Proliferator-Activated receptor a (PPARalpha) plays a crucial role in mediating the effects of fatty acids and fibrates on plasma and cellular lipid metabolism by regulating the transcription of key-genes. Disturbances of PPARalpha function may therefore contribute to lipid metabolic diseases.
The purpose of this project is to study the possible involvement of PPARalpha in these metabolic disorders and the molecular and genetic mechanisms implicated.
First, we will determine the structure of the human PPARalpha gene, and characterize its regulatory regions. Second, we will search for PPARalpha isoforms/mutations in normal persons as well as in patients with FCH, hypoalphalipoproteinemia or syndrome X. The mutations identified will be functionally assayed for transcriptional activity. In parallel, we will study the regulation of PPARalpha expression in human liver and primary cell cultures. Finally, we will clone the human PPARalpha gene promoter and determine its function and regulation. Polymorphic sites in this region will be searched and the possible effects of the sequence variations identified will be analyzed
Training content (objective, benefit and expected impact)
The applicant will benefit from the excellent scientific and technical knowledge of an important European research group in the field of atherosclerosis and lipid metabolism. She will have the opportunity to learn many different molecular biology, biochemistry, cell biology and genetic techniques which will complete her post-graduate formation and will allow her to further continue her career in the international scientific community.
Links with industry / industrial relevance (22)