Project Reference: ICS27-BIO-SB1
Project title: Using AI-based methods for rational design of mRNA coding sequences
Project outline
Our ability to express and purify proteins in other species is of critical importance for both research and biomedical applications such as the production of human insulin in E. coli. However, whether a human protein is expressed well in bacteria depends on a range of factors, including its tRNA demand as determined by its coding sequence. A commonly used strategy to increase expression is to replace rare codons by more common synonymous codons but this approach is unreliable and sometimes has detrimental consequences. For instance, it may alter co-translational protein folding, leading to protein aggregation and difficulties purifying the target protein.
In this project, you will address this challenge by developing AI-based approaches to guide sequence design. Our aim is to reliably enhance heterologous protein expression in E. coli, while also gaining new insights into molecular mechanisms that currently limit protein production.
To achieve this, you will:
Benchmark existing foundation models for heterologous protein expression prediction in E. coli.
Build a framework that optimises coding sequences for expression in E. coli.
Validate your model(s) by performing wet-lab experiments to measure protein output.
The project combines expertise in the Bornelöv lab and at Qkine in predicting and measuring protein output. You will have access to state-of-the-art foundation models, challenging expression targets, and wet-lab validation assays. The project will also use in-house data previously collected at Qkine, combined with a publicly available dataset comprising 244,000 partial coding sequences expressed in E. coli. If needed, you will also be able to generate your own high-throughput data to use for model training. To complement data collected in E. coli, transfer learning will enable you to use insights obtained in other species. For this, you will use both in-house and publicly available foundation models such as Evo2, ESM2 and Encodon.
Principal Supervisor
Dr Susanne Bornelöv
Email address: smb208@cam.ac.uk
Department / Partner Institute: Biochemistry
Website: https://www.sblab.uk
Industrial Partner
Qkine Ltd
BBSRC strategic theme
Transformative technologies
Funding and international applicants (How to apply page)
Deadline: Tuesday 8 December 2026
This is a fully funded programme supported by the BBSRC Doctoral Landscape Awards. An offer of a place includes full funding for your stipend (currently £21,805 for the 2026–27 academic year), as well as payment of the University tuition fees. Applicants are not required to apply to any additional funds (i.e. GATES). For the 2027 intake, approximately 25 studentships will be available across the Targeted and iCASE route.
Read more about the Targeted & iCASE studentships, including programme structure, Professional Internships, training and networking.
Important information for applicants
Academic qualifications and supporting documents
International applicants
A limited number of studentships up to 30% of the cohort can be offered to international candidates, including those from the EU and outside the EU. For example, for a cohort of 25 students, up to 7 studentships may be awarded to international candidates. The Cambridge Biosciences DTP will cover the costs of student visas and health surcharge for any international BBSRC DTP students recruited and will also provide funding to cover both fees and a stipend to support living costs.
Before you apply
Before applying, please check the University of Cambridge's entry requirements .
Applicants should normally hold, or be expected to achieve, a high upper second-class honours degree (High 2:1) or its equivalent.
A pass in a UK-equivalent Master's degree in a relevant subject will exceed the University's minimum academic entry requirement.
If you obtained your qualifications outside the UK, please check the University's International Qualifications guidance to confirm the equivalent qualification for your country.