Phd Studentship: Next Generation Enzymatic Assembly Of Peptide Therapeutics

Application deadline: 19/4/24 Research theme: Chemistry How to apply: https://uom.link/pgr-apply-fap This 4 year PhD project is funded by by CoEBio3 direct for this project. Tuition fees will be covered and you will receive a tax free stipend (depending on circumstances) set at the UKRI rate (£19,237 for 2024/25). 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 Most peptides are produced by solid phase peptide synthesis and related chemical methods that are outdated, problematic to scale-up, require large amounts of deleterious reagents and solvents that are damaging to the environment.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 be run in collaboration with industrial partners at AstraZeneca, GSK, Merck and Codexis. Together we 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 synthetase 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 the scale-up of processes for producing target peptides using novel separation methods to isolate peptide products. Training will be provided in biological chemistry and biochemistry, including protein engineering, directed evolution, enzyme characterisation (X-ray crystallography and AI based modeling) 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. Professor Jason Micklefield will supervise the project which will also involve close interactions with scientists at Merck, GSK, AstraZeneca and Codexis. 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. Before you apply, please send a brief cover letter, CV (no page limit), and the names of at least two referees should be sent by email to both jason.micklefield@manchester.ac.uk and sarah.shepherd@manchester.ac.uk.