Cel The normal expression of genes is tightly regulated. Modifications on histones or on DNA play a central role in the control of gene expression and errors in their regulation often result in diseases such as cancer. These modifications can recruit proteins that regulate chromatin function. Since chromatin is a large macromolecular assembly, modifications most likely act in a concerted manner. However, it is still unclear how the information encoded in combinatorial modification patterns on the DNA and histones is translated into biological signals.My aim is to understand how combinations of DNA and histone modifications regulate the activity of chromatin. I will employ the tools of chemical biology, biochemistry and proteomics in conjunction with tissue culture models in order to identify proteins that can recognise DNA and histone modification patterns in the context of chromatin.I propose to use native chemical ligations to generate a library of histone proteins that carry combinations of modifications that are known to mark specific genomic loci. These histones will be assembled into chromatin together with methylated DNA in order to mimic functional genetic elements such as heterochromatin, promoters or enhancers. I will use the recombinantly defined chromatin in chromatin modification, chromatin remodelling and SILAC affinity purification assays in order to identify novel factors that recognise combinatorial modifications. The SILAC affinity purifications will be linked to a primary cell cancer model in order to identify factors that regulate central tumour suppressor genes. The identified factors will be further characterised in vivo, in vitro and in structural studies in order to understand their molecular function. These experiments will identify factors that can read epigenetic signatures contained in chromatin modification patterns. These constitute the primary targets for “epigenetic drugs” that intervene at key stages in the development of cancer. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsepigenetics Program(-y) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Zaproszenie do składania wniosków ERC-2012-StG_20111109 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Wkład UE € 967 111,45 Adres INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Niemcy Zobacz na mapie Region Bayern Oberbayern München, Landkreis Rodzaj działalności Research Organisations Kontakt administracyjny Ertel Juergen (Dr.) Kierownik naukowy Till Bartke (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (2) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Niemcy Wkład UE € 967 111,45 Adres INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Zobacz na mapie Region Bayern Oberbayern München, Landkreis Rodzaj działalności Research Organisations Kontakt administracyjny Ertel Juergen (Dr.) Kierownik naukowy Till Bartke (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Zakończenie uczestnictwa Zjednoczone Królestwo Wkład UE € 662 518,55 Adres SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Zobacz na mapie Region London Inner London — West Westminster Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Tatjana Palalic (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych