Objective "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." Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesgeneticsRNA Programme(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) Topic(s) ERC-AG-LS6 - ERC Advanced Grant - Immunity and infection Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution KOBENHAVNS UNIVERSITET EU contribution € 1 641 930,80 Address NORREGADE 10 1165 Kobenhavn Denmark See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Principal investigator Kenn Gerdes (Prof.) Administrative Contact Tine Mathiesen (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all KOBENHAVNS UNIVERSITET Denmark EU contribution € 1 641 930,80 Address NORREGADE 10 1165 Kobenhavn See on map Region Danmark Hovedstaden Byen København Activity type Higher or Secondary Education Establishments Principal investigator Kenn Gerdes (Prof.) Administrative Contact Tine Mathiesen (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSITY OF NEWCASTLE UPON TYNE Participation ended United Kingdom EU contribution € 813 179,20 Address KINGS GATE NE1 7RU Newcastle Upon Tyne See on map Region North East (England) Northumberland and Tyne and Wear Tyneside Activity type Higher or Secondary Education Establishments Administrative Contact Amanda Gregory (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data