Objective Antimicrobial resistance is recognised as one of the greatest threats to human health worldwide. Multidrug efflux pumps play a major role in the development of drug resistance in bacterial pathogens. These pumps are able to actively export remarkably broad collections antibiotics and biocides out of the cell. Multidrug efflux pumps have classically been organised into five distinct families or superfamilies. Due to their importance, representative proteins from each of these families have been extensively studied.Using a combination of functional genomics and biochemical methods to study antimicrobial resistance in the hospital pathogen Acinetobacter baumannii, I recently identified AceI, the founding member of a sixth family of multidrug efflux pumps called the Proteobacterial Antimicrobial Compound Efflux (PACE) family. The PACE family is the first new family of efflux pumps to be described in 15 years. In light of its recent identification, there is a paucity of fundamental data describing how PACE family pumps mediate drug efflux. This proposal will apply in vitro biochemical, biophysical and structural analyses to reveal molecular details of the structure and functional transport mechanism operating in PACE family pumps.This proposal will draw on the diverse collective expertise of my Fellowship Supervisor Prof Peter Henderson and his expert colleagues in membrane protein structural analyses and biophysics. In conducting this research I will build lasting collaborative links with these experts that will extend beyond the duration of this fellowship. I will receive specialised training in powerful membrane protein analysis methods that are essential to my career goal of establishing a leading research laboratory examining membrane transport proteins, from regulation to molecular mechanisms. My laboratory vision is to develop novel strategies to interfere with drug efflux pump function and so overcome resistance conferred by this important class of proteins. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance Keywords antimicrobial resistance multidrug efflux membrane transport Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITY OF LEEDS Net EU contribution € 195 454,80 Address WOODHOUSE LANE LS2 9JT Leeds United Kingdom See on map Region Yorkshire and the Humber West Yorkshire Leeds Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80
