Extending the chemical space of mAb based cancer treatment with DNA nanostructures

The Schools of Medicine and Chemistry are offering a fully funded four-year PhD studentship in interdisciplinary cancer research, starting in September 2024. The highly motivated student will receive high-level interdisciplinary training in DNA and monoclonal antibody chemistry and immunology, investigating the synthesis and evaluation of a modular cancer therapy platform.

We propose to develop DNA nanopores into a modular platform that allows them to act as a drug carrier to enhance the efficacy of immunotherapy drugs. Increasing numbers of immunotherapy drugs (such as monoclonal antibodies) have been incorporated into the up-front treatment of multiple types of cancers in the last 20 years. But in most cases, their anti-cancer activity is modest, and they need to be given in combination with chemotherapy. Drug resistance is common and immune-related side effects are frequent due to the binding of the antibodies to non-cancer cells. Our modular platform will involve the conjugation of a nanopore to two monoclonal antibodies: a direct-targeting antibody to focus binding to cancer cells, and an immune-stimulating antibody to drive localised stimulation of host immune cells, thus enhance cancer-killing. The overall aim of this project is to produce potent, targeted anti-cancer immunotherapy drugs with limited toxicity in patients.

There are 3 objectives: 1) Design and synthesis of a simplified and stable DNA nanopore, 2) synthesis of a cleavable linker for attachment to the immune-stimulating antibody, and 3) combining the modular system for in vitro functional studies.

The successful candidate will undertake the four-year Integrated PhD programme ‘Biomedical Science’ commencing 23rd September 2024. The programme is 1 year MRes + 3 years PhD. In year 1 you will choose three rotation projects, alongside taught modules and practical training. In years 2-4 you undertake your PhD. More information is provided here: https://www.southampton.ac.uk/medicine/postgraduate/research_degrees/degrees/iphd-biomed.page.

The successful candidate is likely to have the following qualifications:

• A 1^stor 2:1 degree in a relevant discipline and/or second degree with a related Masters. 

Administrative contact and how to apply:

Please complete the University’s online application form, which you can find at

https://student-selfservice.soton.ac.uk/BNNRPROD/bzsksrch.P_Login?pos=9978&majr=9978&term=202425

You should enter Professor Sean Lim  as your proposed supervisor. To support your application provide an academic CV (including contact details of two referees), official academic transcripts and a personal statement (outlining your suitability for the studentship, what you hope to achieve from the PhD and your research experience to date).

Informal enquiries relating to the project or candidate suitability should be directed to Professor Sean Lim ([email protected]), Dr Eugen Stulz ([email protected])