Objective "The evolution of antibiotic resistance poses an important threat to human health and welfare. Antibiotic resistance is accompanied by fitness costs that have been shown to play a key role in the spread of resistance. These costs are variable, but the underlying ecological and genetic causes of this variation remain obscure. Unfortunately, bacteria can adapt to the cost of resistance by compensatory mutations, and this permits resistance to be maintained in pathogen populations after antibiotics have been withdrawn from use. Resistance mutations vary in their potential for compensatory adaptation, but the causes of this variation remain unknown. In this project, we will determine how the molecular mechanisms of antibiotic resistance and the (i) ecological and (ii) genetic context in which resistance evolves interact to determine (a) the fitness costs associated with antibiotic resistance and (b) the potential and mechanisms for adaptation to the cost of resistance. Conceptually, we will approach this problem using an interdisciplinary approach that combines theory from population genetics and systems biology into the same evolutionary framework. To carry out this research program, we will use high-throughput experimental evolution of resistance to the broad-spectrum antibiotic rifampicin in bacteria from the genus Pseudomonas. This research approach will allow us to measure both the costs of resistance and the (i) rate and (ii) mechanisms of compensation for this cost at an unprecedented scale. The results of this research program will provide key insights into the underlying drivers of resistance emergence and persistence, and it may ultimately be possible to apply the insights from this research program to help combat resistance in pathogen populations. At a more conceptual level, this research will provide an important experimental test of the roles of chance, necessity, and historical contingency in shaping the rate and mechanisms of adaptation." Fields of science natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance 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-SG-ID1 - ERC Starting Grant Interdisciplinary Panel Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Address Wellington square university offices OX1 2JD Oxford GB See on map Activity type Higher or Secondary Education Establishments projects.administrative_contact Gill Wells (Ms.) projects.principal_investigator Roderick Craig Maclean (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 1 196 639,00 Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD GB EU contribution € 1 196 639,00 Address Wellington square university offices OX1 2JD Oxford See on map Activity type Higher or Secondary Education Establishments projects.administrative_contact Gill Wells (Ms.) projects.principal_investigator Roderick Craig Maclean (Dr.) Links Contact the organisation Opens in new window Website Opens in new window
