Targeting RNA modification for modulation of immune cell function

Academic Supervisor: Claudia Ribeiro

Industrial Partner: Storm Therapeutics

The Babraham Research Campus (BRC) is pleased to announce that it has available a number of studentships from its BBSRC Collaborative Training Partnership (CTP) Award to start in October 2025. The BRC CTP is a joint partnership between the Babraham Institute, the BBSRC and BRC and a range of innovative tenant companies on the Campus working in the Bioscience for Health BBSRC priority area. The goals of the BRC CTP are (i) to train excellent PhD students in the advancing frontiers of bioscience discovery and the Bioscience for an integrated understanding of health priority areas and to provide them with a range of scientific and transferable skills; (ii) to give them ‘real-world’ experience of working in the commercial bioscience sector through their respective collaborative PhD projects and (iii) thereby train the next generation of researchers, skilled in modern techniques, critical thinking and business skills. The distinct features and location of the BRC will provide students with access to real-world examples of translational activity, innovation and entrepreneurship and will lead to future careers in academia, industry and science-based tech transfer and commercialisation.

The Babraham Institute is a world-leader in fundamental biological research investigating the systems that underpin development and healthy ageing. It is a recognised postgraduate University Partner Institute of the University of Cambridge. This BRC CTP Studentship, starting October 2025, will be available leading to a University of Cambridge PhD degree in the laboratory of Dr Claudia Ribeiro Claudia Ribeiro » Babraham Institute. This studentship is awarded for 4 years.

Details of our interactive scientific programmes can be found on www.babraham.ac.uk. As a student at the Institute, you will have access to all of our outstanding science facilities, each one providing specialist equipment and expertise to support key research techniques and technologies. 

Project Details

This PhD studentship aims to explore the potential of targeting mRNA translation as a strategy to regulate B-lymphocyte function. The project will be carried out as a partnership between the Ribeiro Lab at the Babraham Institute and Storm Therapeutics, a Babraham Research Campus biotechnology company focusing on the discovery and development of novel small molecule therapies targeting RNA modifying enzymes.

Targeting mRNA translational control is increasingly recognized as a strategy to restrain cancer development. Either because cancer cells require global elevation of protein synthesis or the translation of specific mRNAs for survival, their reliance on the translation machinery constitutes a vulnerability. Likewise, the differentiation of B-lymphocytes into antibody-secreting plasma cells involves steps of abundant translational activity, culminating on the production and secretion of immunoglobulins in vast amounts. Therefore, control over protein synthesis beholds promise for therapeutic intervention – either to improve response to vaccination, reduce exacerbated B-lymphocyte responses in autoimmune disease or to selectively target B-lymphomagenesis.

Recent work carried out in the Ribeiro Lab revealed that B-lymphocyte proliferation and production of high-affinity antibodies is strongly dependent on the availability of a subset of transfer RNA (tRNA) molecules that undergo splicing as part of their maturation process. tRNAs bring amino acids to the nascent polypeptide chain on the translating ribosome and it has long been recognised that efficient protein production depends on a ‘perfect match’ between mRNA codon content and cognate tRNA concentrations (‘codon optimality’). Likewise, the presence of chemical modifications on tRNAs (some of which dependent on tRNA splicing taking place) have been shown to have an impact on the stability and decoding capacity of these molecules. However, the composition of tRNA pools in differentiating B-lymphocytes and how this is modulated to meet the protein synthesis demands associated with antibody production is currently poorly defined.

The PhD candidate working on this project will use state-of-the-art methodology to profile changes in tRNA abundance and chemical modifications underpinning mouse B-lymphocyte differentiation. The role of specific tRNA modifications will be studied using small molecule inhibitors targeting key RNA modifying enzymes developed by Storm Therapeutics. These studies will be performed using ex vivo cultures of primary mouse B-lymphocytes and in vivo mouse immunization protocols established in the Ribeiro Lab.

The PhD candidate will develop conceptual and technical competencies in molecular and cellular Immunology, with a focus on tRNA biology, mRNA translation and B-lymphocytes. The PhD candidate will develop skills in high-throughput sequencing, multi-parameter flow cytometry, and bioinformatics. It is expected the PhD candidate will spend up to 18 months in Storm Therapeutics (located in the same research Campus as the Babraham Institute) to develop skills in in vitro pharmacology, learn new methodology and establish close links with industry.

Keywords: RNA chemical modification, lymphocytes, immune regulation

How to Apply

All applications for PhD Studentships at the Babraham Institute need to be made using the University of Cambridge Graduate Application Portal ( https://www.postgraduate.study.cam.ac.uk/application-process/applicant-portal-and-self-service-account ) regardless of funding source. Please see the “Applying for a PhD” pages on our website ( https://www.babraham.ac.uk/) for further details of the application process.

We hope to be able to invite short-listed applicants to attend our Institute for a series of interviews shortly after the application deadline. This will give applicants an opportunity to meet their Group Leader and their research group, as well as receiving a tour of our research facilities. Reasonable travel expenses will be paid to those invited.

Students will not be able to take up an award unless they meet all University eligibility criteria and are successful in securing admission to the University. In addition, they will not be able to apply for a visa (if needed) until they hold an unconditional offer from the University.

The deadline for submission of applications via the Graduate Application Portal is 24^th November 2024. Incomplete applications will not be considered.

If you would like more information, or have any questions not answered on our website here ( https://www.babraham.ac.uk/work-and-study/phd-programme/phd-applications ), please contact us: The Graduate Studies Programme Administrator, email babraham.graduate@babraham.ac.uk .

An equal opportunities employer. An Institute supported by the Biotechnology and Biological Sciences Research Council.