AstraZeneca funded Non-clinical PhD Studentship in Improved peptides co-translational separation polyprotein

Position: AstraZeneca funded Non-clinical PhD Studentship 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  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  Stop Go . 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.

Candidate We are looking for a highly motivated and enthusiastic individual capable of thinking and working independently. Applicants should have or shortly expect to obtain a first or upper second-class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject such as Biochemistry, Microbiology, Cell Biology or Genetics. These positions are open to UK citizens or overseas students who meet the UK residency requirements (home fees) or are able to augment the funds to cover the extra costs associated with international student fees through scholarships or funding schemes.

Students will not be allowed to supplement fees via self funding.

Full details of the University's entrance requirements and scholarships are specified on the following link: https://, the Department requires that by the time of interview all potential students must have fulfilled the language requirements for admission:  check for further eligibility details using this website: https:// Process All applications should be made online via the University's Applicant Portal for a PhD in Pathology (BLPA
22). A completed application must be submitted by the closing date below. Please also explain your motivation why you wish to pursue a PhD in this area, outline your research interests and background, and describe the qualities and experience you will bring to the role. Please also download our equal opportunities monitoring form from this link and return the completed form by email to postgrad.ac.ukAn

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