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Engineering Immune Cell Surfaces

Primary Supervisor: Professor Matthew I. Gibson, Department of Chemistry

Secondary supervisor: Dr Dan Mitchell, Warwick Medical School

PhD project title: Engineering Immune Cell Surfaces

University of Registration: University of Warwick

Project outline:

In the past decade there has been a revolution in therapeutics with protein and cell based therapies emerging to supplement traditional ‘small molecule’ drugs. These form the so called fourth pillar of chemotherapy, where the body’s own immune system is exploited to fight disease, particularly cancer. One such approach is to use genetic engineering approaches to install antibodies on the surface of T-cells to allow them to recognise cancer cells (CAR-T Chimeric antigen receptor T cells) ; this is crucial as normally T-cells do not actively target or recognise growing tumours. Underpinning this therapy is the need to engineer the cell surface, using genetic techniques.

In this project we will take a revolutionary approach where we use synthetic chemistry to directly modify the surface of cells to introduce new functionality. Site-specific chemistry on cells is challenging, not just due to the diverse range of functionality but also the need for the reactions to all be cyto-compatible. If successful, this will allow cells to be easily modified with functionality not possible using genetic techniques and allow us to understand how surface functionality affects immune-cell function.

The GibsonGroup has recently shown that we can chemical modify glycans (sugars) on the surfaces of cells to install anchors to allow capture of synthetic macromolecules, which can be found here:

  • Optimization and Stability of Cell–Polymer Hybrids Obtained by “Clicking” Synthetic Polymers to Metabolically Labelled Cell Surface Glycans; Biomacromolecules 2019, 20, 7, 2726-2736
  • Engineering Cell Surfaces by Covalent Grafting of Synthetic Polymers to Metabolically-Labelled Glycans, ACS Macro Lett. 2018, 7, 11, 1289-129

This project will enable a student to be exposed to a unique biomaterials environment and learn/apply skills in synthetic biomaterials but also cell biology and advanced analytics, using confocal microscopy and flow cytometry. The GibsonGroup has unique facilities enabling such an ambitious cross-disciplinary project.

Key objectives will include;

  • Investigation of residence time of synthetic surface modifications compared to genetically induced modifications
  • Introduce new functionality to capture native antibodies
  • Demonstrate new immune cell function, not possible using genetic methods

BBSRC Strategic Research Priority: Understanding the Rules of Life

Techniques that will be undertaken during the project:

  • Cell culture
  • Confocal microscopy
  • Flow Cytometry
  • Polymer synthesis
  • Analytical Chemistry
  • Immunological assays

Contact: Professor Matt Gibson, University of Warwick