Obiettivo 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. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsepigenetics Programma(i) 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) Argomento(i) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Invito a presentare proposte ERC-2012-StG_20111109 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Contributo UE € 967 111,45 Indirizzo INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Germania Mostra sulla mappa Regione Bayern Oberbayern München, Landkreis Tipo di attività Research Organisations Contatto amministrativo Ertel Juergen (Dr.) Ricercatore principale Till Bartke (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Germania Contributo UE € 967 111,45 Indirizzo INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Mostra sulla mappa Regione Bayern Oberbayern München, Landkreis Tipo di attività Research Organisations Contatto amministrativo Ertel Juergen (Dr.) Ricercatore principale Till Bartke (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Partecipazione conclusa Regno Unito Contributo UE € 662 518,55 Indirizzo SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Mostra sulla mappa Regione London Inner London — West Westminster Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Tatjana Palalic (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato