PhD Studentship in Chemical Biology

Applications are invited for a PhD studentship focusing on the discovery of dehalogenase enzymes for pesticide detection and removal. The student will be based in the Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, under the supervision of Professor Jason Micklefield. The project is in collaboration with the Grantham Institute and starts on the 29th of September 2025. Tuition fees and stipend at the standard UKRI/London rate are provided. Home and international candidates are both eligible to apply.

Many pesticides contain halogen atoms, particularly chlorine and fluorine, as part of their molecular structure. Although the use of some halogenated pesticides has been restricted, they continue to be widely used in the Global South due to being cheaper and more readily available. Moreover, many of the newly approved agrochemicals and pharmaceuticals contain halogens which can contribute to their persistence in the environment, causing long-term ecological damage and health problems to both wildlife and humans. This persistence arises because microorganisms and plants in the environment generally lack enzymes capable of degrading halogenated compounds.

In this project, we will use genome mining (bioinformatics) methods to identify previously uncharacterised dehalogenases. AI-based tools will help predict the structure, activity, and substrate scope of these new enzymes. The most promising candidates will be tested for dehalogenase activity. Directed evolution will then be conducted to enhance activity, robustness, and substrate versatility towards the specific halogenated scaffolds found in common pesticides.

Our lab is at the forefront of the discovery, characterisation, and engineering of enzymes for biotechnological applications (see below). This PhD project will provide training in organic chemistry and biochemistry, including protein engineering, directed evolution, enzyme characterisation (X-ray crystallography and AI-based modelling), and enzyme assays. PhD candidates are not expected to have expertise in all these areas at the outset; above all, scientific curiosity and a desire to work in a multidisciplinary environment are most important.

Candidates with a degree in Chemistry, Biochemistry, Biological Sciences, or a related science, who also possess a desire to do cutting-edge research at the Chemistry-Biology interface, are encouraged to apply. Applicants should have, or expect to achieve, at least a 2.1 honours degree or a master’s in a relevant science or engineering-related discipline. 

Applications including a brief cover letter, CV (no page limit), and the names of at least two referees should be sent by email to j.micklefield@imperial.ac.uk by the deadline, Friday the 25th of April, 2025.

Examples of related research and links from the Micklefield lab:

Cryptic enzymatic assembly of peptides armed with β-lactone warheads.  Xu et al. Nature Chem Biol 2024, 20, 1371–1379. https://doi.org/10.1038/s41589-024-01657-7

Enzymatic synthesis of peptide therapeutics. Xu & Micklefield Nature Chem Biol 2024, 20, 1256–1257. https://doi.org/10.1038/s41589-024-01658-6

Discovery, Characterisation and Engineering of Ligases for Amide Synthesis. Winn et al Nature 2021, 593, 391–398. https://doi.org/10.1038/s41586-021-03447-w

Merging Enzymes with Chemocatalysis for Sustainable Amide Bond Synthesis. Bering et al Nature Commun. 2022, 13, 380. https://doi.org/10.1038/s41467-022-28005-4

Programmable late-stage C−H bond functionalization enabled by integration of enzymes with chemocatalysis. Craven et al. Nature Catalysis, 2021, 4, 385–394.

https://doi.org/10.1038/s41929-021-00603-3

https://www.micklefieldlab.chemistry.manchester.ac.uk

https://www.imperial.ac.uk/chemistry/

https://www.youtube.com/watch?v=EPUNhcfKtKU

https://www.youtube.com/watch?v=qwvvTEa0ehk

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