Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).
Understanding the Molecular Mechanisms of Antimicrobial Resistance
Secondary Supervisor(s): Depending on the project there are a number of colleagues who would be most appropriate for co-supervision, including but not limited to David Roper, Allister Crow, Seamus Holden, Liz Fullam, Chris Dowson, Alex Cameron, Greg Challis, Chris Rodrigues, Andrew Lovering, Tim Knowles (Birmingham), Roslin Bill, Alan Goddard, Doug Browning, Alice Rothnie (Aston)
University of Registration: University of Warwick
BBSRC Research Themes:
Project Outline
Drug resistant bacteria, including Mycobacteria tuberculosis (Mtb), are one of the leading causes of death worldwide and reflect a serious global health challenge. These bacterial pathogen kills more people than malaria and HIV combined, and are increasingly developing resistance to many of the current front-line drugs. We therefore urgently need to develop new therapeutics.
To do this we need to understand the structural and dynamic basis of the macromolecular drug targets within these drug resistant bacteria. The outer coat of these microbes is extremely complex and form the front-line to a bacterium’s defence. Interwoven within this bacterial cell envelop is a complex mixture of proteins, lipids and sugars.
The development of accurate protein-folding software, such as AlphaFold, has enabled the computational determination of over 130 million monomeric protein structures. One can also use this method to model both homo- and heteromeric complexes. This is especially true for bacterial proteins, where organism and operon-based information may be used to provide a blueprint for how the folding methods may assemble the protein structure and/or complex.
The overall aim of this proposal is to provide a structural and dynamic description of bacterial complexes that are involved in key bacterial processes and resistance within the cell envelope.
By understanding the three-dimensional details of how these complexes form and move, we have a better grasp of the fundamental processes performed by these proteins. This therefore provides an improved understanding of how one can develop novel antimicrobial inhibitors.
References
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