Design of highly effective immunogens for development of monoclonal antibodies to self-peptides: simulation and experiment

Monoclonal antibody (mAb) therapy is an immunotherapy that uses highly specific antibodies to bind to particular secreted or cell-surface proteins, in order to stimulate the immune system to destroy those cells. This type of therapy can therefore be used to specifically target cancers. The process involves binding peptides derived from tumours to nanoparticles. A challenge is to optimise the interactions between the peptides and nanoparticles to ensure that key epitopes are exposed to the environment and free to stimulate spleen cells to create the antibodies that will target the cancer.

In this project we will use biomolecular simulation to study the binding process, and to design peptide sequences that not only optimise the adsorption but also enhance the immune system recognition utilising a recently discovered, patentable process. The designed peptide-nanoparticle conjugates will be tested experimentally, and if successful our strategy will yield new technology of immense impact. The industrial partner for this project, The Antibody Company, will be able to utilise the technology in their portfolio of antigens, and the project includes a 6-month placement working in the company to develop monoclonal antibodies for its targets.

The simulation work will be undertaken in Dr Paul Mulheran’s group in the Department of Chemical and Process Engineering at the University of Strathclyde, utilising the ARCHIE-WeSt research computing centre (www.archie-west.ac.uk). The experimental work will primarily be performed in Dr Val Ferro’s laboratory in the Strathclyde Institute of Pharmacy & Biological Sciences (SIPBS). Other collaborators on the project include Dr Karina Kubiak-Ossowska (ARCHIE-WeSt), Prof. Alex Mullen (SIBPS), Dr Mark Williams (Glasgow Caledonian University), and Dr Richard Soutar (Beatson West of Scotland Cancer Centre, University of Glasgow).

This PhD studentship is fully-funded for 4 years, and is part of the 2018 cohort for the Industrial Biotechnology Innovation Centre’s Collaborative Training Partnership (www.ibioic-ctp.com) funded by the BBSRC. The programme provides its students with the professional and research skills required to contribute to the growth of biotechnology in the UK. In addition, the PhD student will also register for the Postgraduate Certificate in Researcher Development (PGCert), which is a supplementary qualification that develops a student’s skills, networks and career prospects.