Cel The DNA of eukaryotic cells is packaged in chromosomes located in the nucleus. The fundamental package unit of DNA are nucleosomes, which are composed of an octameric histone core that is wrapped with DNA. Over the last few years a wide variety of post-tra nslational modifications of these histone proteins have been linked to essential biological processes. This is particularly true of histone acetylation, by enzymes called histone acetyl-transferases (HATs). Acetylation of lysine residues can activate gene transcription, whereas conversely deacetylation is linked to gene repression. Thus, the modification of histones in chromatin plays a central role in transcription regulation. Currently the dissection of the roles of individual modified histone lysine resi dues is limited by low activity and/or specificities of isolated/recombinant HATs. We propose to combine directed evolution with biochemical and in vivo assays to understand the functional consequences of modifying specific histone lysine residues. We will use natural HATs as starting points to evolve novel HATs that have enhanced activities and altered specificities. These engineered HATs will be used to generate histone with specific acetylation patters, which will permit reconstitution of defined chromat in templates to probe the biological function of histone acetylation in detail.The proposed research project will lead to a better understanding of how chromatin modification and physiological responses are related. This knowledge is instrumental to fully understand how eukaryotic organisms turn on and off gene transcription by chemical modification of histones. Thus, the proposed fellow will contribute to EU scientific excellence by starting a new area of research in the field of chromatin function. Detail ed insights into these mechanisms are very likely to provide new targets for gene transcription inhibition and are thus of great importance for the pharmaceutical and medical community. Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Program(-y) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Temat(-y) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Zaproszenie do składania wniosków FP6-2002-MOBILITY-5 Zobacz inne projekty w ramach tego zaproszenia System finansowania EIF - Marie Curie actions-Intra-European Fellowships Koordynator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Wkład UE Brak danych Adres The Old Schools, Trinity Lane CAMBRIDGE Zjednoczone Królestwo Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych
