PhD Studentship - Enzyme Cascades Controlled in the Electrochemical Leaf for Discovery in Antimicrobial Strategy

Research theme: Electrochemical control of nanoconfined enzymes

How to apply: uom.link/pgr-apply-fap

This 3.5 year PhD project is funded by the Department of Chemistry. The funding is open to home students only. Funding covers tuition fees and provides a tax free stipend set at the UKRI rate (£18,622 for 2023/34).

Antibiotic discovery is usually aimed at single entities, for example a bacterial enzyme or efflux protein. This also means that antimicrobial resistance (AMR) mechanisms are considered in terms of the individual response, for example, mutations in a single target enzyme, affording resistance to the drug. But the inherent synergy between the multi-enzyme cascades of bacterial metabolism offers a new way to target bacteria.

This project will exploit the Electrochemical Leaf (e-Leaf), (a disruptive electrochemical platform in the field of protein film electrochemistry that enables the electrification and control of multi-enzyme systems), to discover new antimicrobial strategies aimed at targeting multi-enzyme cascades and the inherent teamwork in bacterial metabolism.

The e-Leaf (1-6) is a new invention that enables multi-enzyme cascades to be electrically driven and controlled when loaded into a highly porous metal oxide electrode. Central to the science, is a key photosynthetic enzyme, ferredoxin NADP+ reductase (FNR), bound tightly inside the electrode pores, where, by controlling the applied voltage, fast bidirectional electron exchange between its active site flavin and the electrode, enables it to catalyse the interconversion of NADP+/NADPH. The co-entrapment of an enzyme that requires NADP(H), facilitates electrical connection to FNR through NADP(H) recycling – this is the gateway to enable the electrification and control of extended multi-enzyme cascades. The crowded electrode pores mirror the environment in which enzymes function in nature that leads to high catalytic efficiency (for example, inside highly crowded organelles such as the mitochondria or chloroplast) and yields authentic enzymological insight.

This research is interdisciplinary, and will involve training in bio-electrochemistry, enzyme biochemistry, enzyme engineering, molecular biology, and electrode fabrication.

Informal enquires about this research are welcome, please contact Dr. Clare Megarity (clare.megarity@manchester.ac.uk).
scholar.google.com/citations?user=8trlHr8AAAAJ&hl=en

Applicants should have, or expect to achieve, at least a 2.1 honours degree or a master’s (or international equivalent) in a relevant science or engineering related discipline.

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