PhD Studentship in Chemical Biology

Applications are invited for a four year PhD studentship, starting 29^th September 2025, funded by the European Research Council (ERC) project Enzymatic Methods for Peptide Synthesis (EZYPEP). The student will be based in the Department of Chemistry, Molecular Sciences Research Hub, Imperial College, under the supervision of Professor Jason Micklefield. Tuition fees will be covered and you will receive a tax free stipend set at the UKRI-London rate.

Peptides are essential in life and are widely used as therapeutic agents, vaccines, biomaterials and in other important applications. Currently there are more than 80 peptide drugs approved world-wide, with many more in clinical trials, including essential antibiotics, antiviral and anticancer agents as well as treatments for diabetes. Most peptides are produced by solid phase peptide synthesis and related chemical methods that are outdated, problematic to scale-up, require large amounts of deleterious reagents and solvents that are damaging to the environment. In this PhD project we will address this problem by developing novel enzymatic methods for more sustainable, cleaner and scalable peptide assembly. The project will focus on developing next generation enzymatic peptide assembly technology that can deliver valuable pharmaceuticals ranging from small peptide drugs through to larger antibody drug conjugates (ADC). The PhD research programme will include: (i) using bioinformatics approaches to discover new ligases and other enzymes from nature, that facilitate peptide assembly and functionalisation; (ii) developing directed evolution approaches to improve the activity and substrate scope of the enzymes for peptide assembly; (iii) optimising processes for producing target peptides using novel separation methods to isolate peptide products.

Training will be provided in organic chemistry and biochemistry, including protein engineering, directed evolution, enzyme characterisation (X-ray crystallography and AI based modelling) and enzyme assays. 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 jason.micklefield@manchester.ac.uk (Deadline for applications is Monday the 18th November)

Please note the Micklefield lab will be based at Imperial College, London from the 1^st of December 2024.

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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