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The structure and molecular mechanism of transport proteins within the PACE family of multidrug efflux pumps

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2015

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Coordinator

UNIVERSITY OF LEEDS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 195 454,80
Address
WOODHOUSE LANE
LS2 9JT Leeds
United Kingdom

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Region
Yorkshire and the Humber West Yorkshire Leeds
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 195 454,80
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