Michael Woodmancy

Profile

I studied at the University of Leeds in the Faculty of Biological Sciences from 2016-2021, achieving an MBiol Microbiology (IND) 1st class with Hons. For my final year project, I worked with Dr. Jamel Mankouri, Dr. John Barr and Dr. Martin Stacey to develop and screen a Rabies ‘pseudovirus’ to identify possible targets for a future antiviral therapy.

Research interests

Given the threat of antimicrobial resistance (AMR), there is an urgent need to identify targets to inspire development of novel antibiotics. Nine of the twelve bacteria that pose the greatest threat to human health are gram-negative (according to the World Health Organisation), but only two antibiotics are in clinical development against these pathogens, representing a risk to human health. The outer membrane (OM) of gram-negative pathogens acts as a first line of defence against antibiotics, making it key for bacterial survival and AMR. Finding ways to perturb OM assembly may sensitise gram-negative bacteria to current antibiotics, or reveal new targets for antibacterial development, providing routes to overcome AMR. We have been studying a key chaperone in OM assembly called SurA and identified hotspots/residues responsible for its function, thus uncovering sites for targeting by small molecules that could be precursors to novel antibiotics. SurA plays important roles in virulence, pathogenicity, and sensitivity to antibiotics, demonstrating that it is an excellent target for novel antibiotics. In my project I’m using established virtual high-throughput screening (vHTS) methods with large (>10million) commercially available small molecule libraries to identify putative SurA binders that interact with key functional hotspots. Hits from these screens will then be validated using a combination of in vitro functional assays and biophysical tools (e.g. SPR, fluorescence, NMR, native MS and hydrogen-deuterium exchange-MS). Finally, phenotypic screens will be used to determine if compounds perturb OM assembly and bacterial viability in gram-negative bacteria. The overarching goal of this project is to develop first-in-class small molecules that target SurA chaperone function and interfere with OM assembly. These compounds will represent leads for further development to treat deadly gram-negative bacterial infections.

Qualifications

• MBiol Microbiology
• BSc Microbiology (IND)