Obiettivo Tissue responses to microbial and endogenous danger signals involve the activation of both resident and monocyte-derived macrophages, as well as the coordinated inducible expression of hundreds of inflammatory genes. Gene transcription is controlled by the information contained in thousands of genomic regulatory elements (enhancers and promoters), which is first read by transcription factors (TFs) and then integrated and relayed to the transcriptional machinery via an array of co-regulators with disparate biochemical activities and functions. The recent work of several groups, including our own, has extensively characterized how in macrophages the genomic regulatory sequences controlling inflammatory gene expression are coordinately bound and activated by myeloid lineage-determining TFs and broadly expressed stimulus-activated TFs. However, we still have a very incomplete understanding of the necessary next step in the process, namely how distinct combinations of DNA-bound TFs regulate recruitment and function of the co-regulators and machineries that control gene transcription. Here, I propose to systematically identify the complement of co-regulators that control the induction of inflammatory genes in macrophages, which will be then mechanistically and functionally characterized both in vitro and in vivo. By integrating cutting edge genomic and computational approaches with focused genetic screens and biochemical analyses, and eventually validating relevant results in mouse models, this project aims at obtaining an unprecedented level of understanding of the information flow linking genomic regulatory elements to inflammatory gene transcription. Campo scientifico natural sciencesbiological sciencesgenetics Parole chiave Macrophages transcription transcription factors chromatin epigenetics and gene regulation Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-ADG-2015 - ERC Advanced Grant Invito a presentare proposte ERC-2015-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante ISTITUTO EUROPEO DI ONCOLOGIA SRL Contribution nette de l'UE € 1 377 911,71 Indirizzo VIA FILODRAMMATICI 10 20121 Milano Italia Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 377 911,71 Beneficiari (2) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto ISTITUTO EUROPEO DI ONCOLOGIA SRL Italia Contribution nette de l'UE € 1 377 911,71 Indirizzo VIA FILODRAMMATICI 10 20121 Milano Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 377 911,71 HUMANITAS UNIVERSITY Partecipazione conclusa Italia Contribution nette de l'UE € 1 122 088,29 Indirizzo VIA RITA LEVI MONTALCINI SNC 20090 Pieve Emanuele Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 122 088,29
