AstraZeneca funded Non-clinical PhD Studentship (Fixed Term) in Improved 2A peptides for co-translational separation of a polyprotein

Applications are invited for a 4-year PhD studentship starting on 1 October 2027 and based in the Department of Pathology, University of Cambridge, and the AstraZeneca Discovery Centre at Cambridge. The student will be working on a collaborative project jointly supervised by Prof. Andrew Firth at the University of Cambridge and Dr Giovanni Ciotta at AstraZeneca and will have the opportunity to work across the two sites. The project focuses on manipulating peptide-bond skipping sequences to aid protein engineering.

2A peptides mediate co-translational separation of a polyprotein via a mechanism known as "ribosome skipping" or "StopGo". These ~20 amino acid peptides adopt an unusual conformation within the translating ribosome that prevents peptide bond formation at a specific site but instead promotes release of the nascent peptide followed by continuation of translation. These sequences have proved to be exceptionally useful in biotechnology because they allow the introduction of all components of a pathway or multi-subunit complex in a single step, with stable stoichiometric co-expression from a single promoter. However, 2A peptides have some caveats - including ribosome drop-off, ribosome pausing/stalling, and some amount of separation failure - which constrain their functional utility. We have identified new classes of 2A sequences, some of which have improved properties compared to traditional 2A peptides. This PhD project will contribute to our work investigating these new 2A sequences and optimising them for biotechnological applications.

The UCam team has expertise in molecular biology including ribosome profiling, ribosome structure and function, cell biology, cryo-electron microscopy, and bioinformatics. The AZ team has expertise in cell therapy, CRISPR/Cas9 technologies, and viral vectors. The PhD project will focus on molecular biology techniques but there will also be opportunity for bioinformatic skill development and there may be scope to obtain structural biology experience. At the AstraZeneca site, the student will focus on implementing optimised sequences in specific biotechnological applications, e.g. in cell therapy.

For full details and application process please click the 'Apply' button above.

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