Cel 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. Dziedzina nauki natural sciencesbiological sciencesgenetics Słowa kluczowe Macrophages transcription transcription factors chromatin epigenetics and gene regulation Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-ADG-2015 - ERC Advanced Grant Zaproszenie do składania wniosków ERC-2015-AdG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-ADG - Advanced Grant Instytucja przyjmująca ISTITUTO EUROPEO DI ONCOLOGIA SRL Wkład UE netto € 1 377 911,71 Adres VIA FILODRAMMATICI 10 20121 Milano Włochy Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Private for-profit entities (excluding Higher or Secondary Education Establishments) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 377 911,71 Beneficjenci (2) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko ISTITUTO EUROPEO DI ONCOLOGIA SRL Włochy Wkład UE netto € 1 377 911,71 Adres VIA FILODRAMMATICI 10 20121 Milano Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Private for-profit entities (excluding Higher or Secondary Education Establishments) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 377 911,71 HUMANITAS UNIVERSITY Zakończenie uczestnictwa Włochy Wkład UE netto € 1 122 088,29 Adres VIA RITA LEVI MONTALCINI SNC 20090 Pieve Emanuele Zobacz na mapie Region Nord-Ovest Lombardia Milano Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 122 088,29