Objetivo "Almost all bacterial species generate persisters, individual cells that are tolerant to antibiotics. Persisters have entered a dormant or slow growing state in which they are recalcitrant to the killing activity of most known antibiotics. The molecular mechanisms underlying bacterial persistence are unknown and there is a pressing need to develop new methods and approaches to study the phenomenon. We discovered recently that RNA endonucleases (RNases) encoded by toxin - antitoxin (TA) genes are required for persistence of the model bacterium Escherichia coli. We have shown that the RNases inhibit translation by cleavage of mRNA or tRNA and that their activation halts cell growth and induces persistence. We propose a testable model in which persistence is induced by stochastic activation of the RNases. Almost all free-living bacteria, including many serious pathogens, have TA genes, often in multiple or even many copies. For example, the major pathogen Mycobacterium tuberculosis, which can persist in the human body for many years, has at least 88 TA loci. This proposal describes a research program dedicated to develop novel general methods to study the persistence phenomenon and to test the hypothesis that TA loci are central to bacterial persistence. The implementation of novel, leading edge technologies will allow a profound understanding of the persistence phenomenon. Mechanistic insight into the persistence problem, in turn, will provide a basis for a rational approach to the development of drugs and drug administration regimes that may improve treatment of persistent infections." Ámbito científico natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesgeneticsRNA Programa(s) 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) Tema(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Convocatoria de propuestas ERC-2011-ADG_20110310 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida KOBENHAVNS UNIVERSITET Aportación de la UE € 1 641 930,80 Dirección NORREGADE 10 1165 Kobenhavn Dinamarca Ver en el mapa Región Danmark Hovedstaden Byen København Tipo de actividad Higher or Secondary Education Establishments Investigador principal Kenn Gerdes (Prof.) Contacto administrativo Tine Mathiesen (Mrs.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo KOBENHAVNS UNIVERSITET Dinamarca Aportación de la UE € 1 641 930,80 Dirección NORREGADE 10 1165 Kobenhavn Ver en el mapa Región Danmark Hovedstaden Byen København Tipo de actividad Higher or Secondary Education Establishments Investigador principal Kenn Gerdes (Prof.) Contacto administrativo Tine Mathiesen (Mrs.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos UNIVERSITY OF NEWCASTLE UPON TYNE La participación finalizó Reino Unido Aportación de la UE € 813 179,20 Dirección KINGS GATE NE1 7RU Newcastle Upon Tyne Ver en el mapa Región North East (England) Northumberland and Tyne and Wear Tyneside Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Amanda Gregory (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
