PhD Studentship: Superselective Targeting of Cancer and Neuronal Cells Using Multivalent Lectin-glycan Interactions

Funding

EPSRC Doctoral Training Partnership Studentship offering the award of fees, together with a tax-free maintenance grant of £19,237 per year for 3.5 years. 

Lead Supervisor’s full name & email address

Professor Bruce Turnbull – w.b.turnbull@leeds.ac.uk

Co-supervisor name(s)

Dr Ralf Richter – r.richter@leeds.ac.uk

Project summary

Are you keen to progress research in glycoscience, at the interface between chemistry, biology and physics, and interested in developing a new type of probes for diagnostics and targeted drug delivery? This project may be for you!

Glycocalyces are glycan-rich coats that surround virtually every cell in our body. They are essential for multicellular life and instrumental for cells to communicate with their environment. How cells use their surface glycans to communicate, however, remains a major open question in biology. Many cell types express a similar set of glycans, and it is the relative abundance of glycan epitopes, rather than the mere presence of a given epitope, that differentiates one cell type from another.

This project aims to develop ‘superselective’ glycocalyx probes that are not only able to recognise a specific glycan epitope, but additionally are also exquisitely sensitive to the density of glycans expressed on the cell surface. If successful, these probes will be able to diagnose and target specific cell types, such as cancer cells, with exquisite selectivity.

We have recently demonstrated that multivalent probes based on a flexible polymer scaffold can effectively discriminate surfaces based on the density of surface receptors (Dubacheva et al, Acc Chem Res, 2023, 56:729). In this project, you will develop new polymer scaffolds for superselective probes based on lectins (glycan-binding proteins) and demonstrate how these can be used to analyse the glycocalyx of cells, such as cancer cells, neurons or the endothelial cells that line the inner walls of our blood vessels. To this end, you will combine synthetic and bio-orthogonal chemistry with protein biochemistry to develop new probes, and evaluate them using cell biology and biophysical techniques. The team of supervisors and collaborators will provide the ideal training environment for this multi-disciplinary project.

By demonstrating feasibility of superselective recognition of selected cell types, this project has the potential to transform the new superselectivity concept into a technology for a wide range of applications, including targeted drug delivery, cell sorting and in vivo imaging and cell diagnosis.

This work is supported by a multi-disciplinary team of supervisors with expertise in all research areas relevant to this project. Excited by this project? Please contact the supervisors for more information before submitting your application.

Relevant references

1. V. Dubacheva, T. Curk and R. P. Richter 2023. Determinants of Superselectivity - Practical Concepts for Application in Biology and Medicine. Acc Chem Res 56:729-739.

Please state your entry requirements plus any necessary or desired background

First or Upper Second Class UK Bachelor (Honours) or equivalent

Subject Area

Biochemistry, Biophysics, Pharmaceutical/Mecidinal Chemistry, Physical Chemistry, Synthetic Chemistry

Advert information