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Next generation glycan arrays

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

Secondary supervisor: TBC

PhD project title: Next generation glycan arrays

University of Registration: University of Warwick

Project outline:

Glycans (aka sugars/carbohydrates) are responsible for a huge range of biological recognition events – from the engagement of a sperm and an egg, to the binding of respiratory viruses, such as influenza and SARS-CoV-2 to the respiratory tracts. It is estimated that 50 % of human proteins are glycosylated. However, due to the low binding affinity of a single glycan-protein interaction and the vast chemical space of glycans, the identification of the binding partner of a new (or known) protein is not trivial. This technology gap means the ‘glycome’ is an exciting, but still not fully explored area of bioscience.

The current state of the art uses elegant microarrays which display 100’s (or more) of glycans and ‘capture’ proteins from solution. However, these require labelling of the protein (or cross- linking of the protein, changing its native state) and are not suited for quick testing of a new target. Finally, glycan arrays are not widely available with few central facilities.

This lack of information for the glycome, also hinders the translation of glycan-binding into innovative diagnostics (and other applications). The GibsonGroup and Iceni have recently demonstrated the principle of glycan-binding for COVID-19 diagnostics, showing the potential of this approach.

ACS Central Science, 2020, 6, 11, 2046 - 2052. The SARS-COV-2 spike protein binds sialic acids, and enables rapid detection in a lateral flow point of care diagnostic device.

This exciting project will leverage the expertise in biomaterials from the GibsonGroup to develop a next generation platform for rapid, low-cost and label-free investigation of glycan-protein interactions.

The project will therefore explore the following:

  • Synthesis and characterization of nanoparticle sensors bearing complex glycans
  • Investigation of how the nanoparticle surface interacts with endogenous (non-specific) compounds such as blood, saliva which may compromise function
    Integrate the nanomaterials into a low-cost platform for single, or multiplexed, rapid evaluation of existing and emerging pathogenic reagents
  • Apply this tool to a range of outstanding glycoscience problems

    BBSRC Strategic Research Priority: Understanding the Rules of Life: Immunology, Microbiology, Neuroscience & Behaviour, Plant Science, Soil Science, Stem Cells & Structural Biology. Integrated Understanding of Health: Ageing, Diet & Health, Pharmaceuticals & Regenerative Biology

        Techniques that will be undertaken during the project:

        • This project is truly interdisciplinary bioscience, combining modern nanomaterials synthesis, to dissect complex biomolecular interactions. The student will have the opportunity to learn synthetic and characterization skills, protein binding assays as well as device development

        Contact: Professor Matt Gibson, University of Warwick