Obiettivo Tuberculosis (TB) is a major global problem that urgently requires new preventive and therapeutic approaches. Only minority of people infected with M. tuberculosis develops active TB. Genetic studies provide an unbiased way to scan the whole human genome to find sequence polymorphisms that predispose to TB. Therefore, we have established the world s largest sample collection for TB genetic studies. Now we genotype 6,000 HIV-negative patients with pulmonary TB and 6,000 healthy controls at ~1 million polymorphic sites across the whole genome. This genome-wide association study (GWAS) will allow us to compare frequency of genetic variants among patients and controls to find genes that protect from TB.Given that susceptibility to TB is a complex disease, a complementary strategy in genetic research is to identify variants that control intermediate cellular phenotypes. Here, for the first time I will undertake a large-scale study to identify polymorphisms that control gene expression in human macrophages, cells that play key role in protection from M. tuberculosis. We will study in vitro global gene expression in uninfected and M. tuberculosis-infected macrophages from hundreds of healthy volunteers correlating it with the genome-wide genotype data of these subjects. This will allow us to identify variants that regulate differential gene expression in macrophages upon M. tuberculosis infection. We will also study functional effects of the polymorphisms associated with TB risk in the previous and ongoing studies. Taken together these experiments will discover genes and biological pathways involved in protection from M. tuberculosis and will characterise macrophage transcription profile of subjects that are genetically predisposed to TB. Campo scientifico medical and health sciencesclinical medicinepneumologytuberculosisnatural sciencesbiological sciencesgeneticsgenomes 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-ID1 - ERC Starting Grant Interdisciplinary Panel Invito a presentare proposte ERC-2010-StG_20091118 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contributo UE € 1 500 000,00 Indirizzo TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Regno Unito Mostra sulla mappa Regione East of England East Anglia Cambridgeshire CC Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Renata Schaeffer (Ms.) Ricercatore principale Sergey Nezhentsev (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Regno Unito Contributo UE € 1 500 000,00 Indirizzo TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Mostra sulla mappa Regione East of England East Anglia Cambridgeshire CC Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Renata Schaeffer (Ms.) Ricercatore principale Sergey Nezhentsev (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
