The skin is the first body defence towards various injuries including UV-rays. The molecular mechanism underlying the UV-response is in part dependant on gene expression modulation implicating the ubiquitous family of USF transcription factors. They have been largely involved as critical UV-activators of genes expression in melanocytes, mediating the UV-induced tanning-response following activation of the stress-responsive p38 kinase. Mitf, the master melanocyte regulator, mediating melanocyte stem cells and melanoma proliferation/differentiation is also a member of the b-HLH-LZ family and is a downstream target of the p38 kinase. How do these transcription factors cooperate to influence skin protection and melanoma progression remains an opened question? The specific aims of the project will be focused on the less documented member the USF-family and are as follow: 1. To determine the role of USF1 at skin level, after UV induction (USF1 KO mice model). 2. To identify the target genes of USF factors at a high level (ChipChip). 3. To correlate USF activity with stress mediated transcriptional regulation and protein modifications. We anticipate that the results will reveal both general principles on USF-target genes and function after UV or environmental stress and also general molecular process implicated in skin-protection and melanoma formation that are regulated at the transcriptional level. The proposal addresses important issues by the use of physiological model in order to identify key pathways for metabolism with long term implications for skin protection and melanoma treatment. The project provides high quality technical and intellectual inputs on the basis of close collaboration and technology transfer with scientific and medical laboratories in France. The project will also give me the high quality level training in technical and complementary scientific competencies required to fulfil my career.
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