PhD Studentship/Marie Sklodowska-Curie ESR: Tuning ADC Payload Release with Active Learning

Fixed-term: The funds for this post are available for 3 years. 

We invite applications for a Marie Sklodowska-Curie Early Stage Researcher (MSC-ESR) Fellowship to work with Professor Goncalo Bernardes on the control of ADC payload release. 

Antibody Drug Conjugates (ADCs) are a rapidly expanding class of targeted therapeutics. Much effort in the field has been devoted to the identification of novel payloads and to engineering monoclonal antibodies. Yet one critical component (the linker) remains comparatively under-explored. Linkers govern the controlled release of potent payloads inside specific cellular environments, and improving linker design is essential for next-generation ADCs. 

This project aims to develop a systematic strategy for tuning payload release rates by modulating the structure of para-aminobenzyloxycarbonyl (PABA) linker units. By altering substituents around the PABA core, we will investigate how electronic and steric effects influence payload pKa and, ultimately, release kinetics under biologically relevant triggers. The successful candidate will work at the interface of organic synthesis, chemical biology, and machine learning to guide linker design and optimise ADC performance against acute myeloid leukaemia (AML). 

Laboratory experiments and machine learning models will be implemented to achieve the following aims:

1. Develop a random forest regression model to predict pKa values of payloads using tabulated steric and electronic descriptors.
2. Synthesize novel PABA-derived linkers and prepare conjugates using model compounds.
3. Measure pKa and release behaviour; iteratively refine ML models with experimental outputs.
4. Apply the workflow to generate an ADC targeting AML, which will be validated using in vitro assays (payload release, cell viability, patient samples) and in vivo disease models.

The project will form part of a EC Marie Sklodowska-Curie Doctoral Training Network (LowDataML), which involves academic and industrial teams across Europe. Although based in Cambridge, the successful candidate will have the opportunity to collaborate with different members of the network, including secondments, yearly summer schools and attendance at international meetings. 

More information about the research in the Bernardes group can be found at: https://www.ch.cam.ac.uk/person/gb453

Applicants must satisfy the EC's eligibility requirements for MSC-ESR Fellowships, and must not have resided in the UK for more than 12 months in the last three years. Candidates should have (or expect to obtain) at least the equivalent of a UK upper second class honours degree (and preferably a Masters degree) in chemistry, biochemistry or related area. The Fellowship is offered in conjunction with a PhD position, subject to the Fellow satisfying the university's admissions requirements for PhD study. The Fellowship will provide a salary that includes a living allowance of around GBP40,000 p.a. plus a mobility allowance of around GBP5,000 p.a.

Applications should include a CV, a half-page summary of any master/diploma thesis, certificates of examination grades, a cover letter (up to 1 page) describing your research career goals, skills and experience, and contact details for at least two academic referees, and should be sent by email to Professor Goncalo Bernardes gb453@cam.ac.uk via the above 'Apply' button. Informal enquiries about the position can also be addressed to Professor Bernardes. 

Information about research in the Department of Chemistry is given at: http://www.ch.cam.ac.uk

Please quote reference MA48239 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live & work in the UK.

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