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In silico design of high-affinity recombinant antibodies


Project Description

Currently there is a trend to move from small drug molecule therapy to use of biologics such as monoclonal antibodies (mAb). MAb therapy uses highly specific antibodies to bind to particular cells or proteins, in order to stimulate the immune system to destroy or neutralise those components that may be involved in disease progression. In a natural immune response, early antibodies bind with low affinity and are less specific about which antigen they bind to. As the immune response continues and there is long-term exposure to an antigen, the antibodies “mature”, as a result of mutations in the binding regions of the antibodies. This leads to an increase or decrease in binding affinity. This provides a blueprint for the computational design of effective antibodies, with the advantage that we do not need to rely on purely random mutations but can be guided by our understanding of the interactions between biomolecules and antigens.

In this project we will use a variety of biomolecular simulation techniques to study the binding process, and to design mutated structures to optimise the binding of the antibody to its antigen, whilst maintaining selectivity. The designed antibody structure will be produced recombinantly and 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 antibodies, and the project includes a 6-month placement working in the company to develop high-affinity 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), along with Dr Karina Kubiak-Ossowska. The experimental work will primarily be performed in Dr Val Ferro’s laboratory in the Strathclyde Institute of Pharmacy & Biological Sciences (SIPBS), in collaboration with Eric Wagner from The Antibody Company.

This PhD studentship is fully-funded for 4 years, and is part of the 2019 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.

Applications must be received by 31st May 2019, and interviews will be conducted in June 2019. The studentship will start 1 October 2019.

Funding Notes

The studentship fully covers the fees and stipend for UK students. EU students are only eligible if they have been resident in the UK for 3 years prior to the start of studentship. Students applying should have (or expect to achieve) a minimum 2.1 undergraduate degree in a relevant engineering/science discipline, and an interest in computational research as well as experimental experience. They should also be highly motivated to undertake multidisciplinary research. Experience of biochemistry techniques will be an advantage.

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