MRC DiMeN Doctoral Training Partnership: Unlocking the tumour glyco-code to transform the diagnosis and treatment of breast and prostate cancer.

Breast and prostate cancer remain leading causes of cancer-related deaths globally and new treatments are urgently needed. This project will focus on exploiting glycans (complex sugars that coat our cells) to develop a new and potentially transformative approach to cancer diagnosis and treatment.

Glycans are commonly linked to proteins (glycoproteins) or lipids (glycolipids) and have fundamental roles in many cellular processes, including fertilisation, determining blood groups, and influencing how a cell responds to biological signals. The myriad roles of glycans are many and diverse, yet we still have so much to learn about them. Tumour cells have a completely different coat of glycans on their cell surface than healthy cells. This unique glycan coat plays a critical role in disease progression (including tumour immune escape, metastasis, and the development of therapy resistance). Accordingly, numerous marketed diagnostics and experimental therapeutics target cancer-associated glycans, and once we a better understanding of the tumour glycome many more will be possible. Studies by us and others indicate there are huge changes to glycans in both breast and prostate cancers and that this can be targeted therapeutically. However, to translate these findings into the clinic, we need a much better picture of how glyco-codes change in cancer and which glycans are best to target for each tumour type and patient.

This multidisciplinary project will focus on targeting glycans to benefit patients with breast or prostate cancer. You will spearhead the use of innovative diagnostic tools to profile the glycome of breast and prostate cancer cells and shed light on the role of cancer-associated glycans in different stages of tumorigenesis. By using diagnostic immunohistochemistry and ELISA assays, you will profile glycosylation changes in clinical tissue and blood samples from patients. Alongside this, utilising immune cell co-cultures, cancer spheroid models, and cutting edge pre-clinical in vivo models you will discover the functional role of glycans in breast and prostate cancer pathology, and test if novel glycan-targeting drugs can be developed as new therapies. The project will utilise a repertoire of recently developed glycosylation inhibitors provided by industrial partners, some of which are already being tested in clinical trials for other indications. The outcome of the project is expected to lead to a functional readout of the tumour glyco-code for breast and prostate cancer that will aid patient stratification and precision treatment.

The project offers a unique opportunity for a student to be trained by a multidisciplinary team with complementary expertise from academia and industry. You will be part of Newcastle University Centre for Cancer, where you will join a team of world-leading cancer researchers and have access to cutting- edge resources and equipment. You will be incorporated into the Munkley research group and will be part of an international team with expertise in cancer glycobiology, biomarker discovery and pre-clinical testing of novel therapeutics. You will also work closely with three industrial partners to ensure the successful delivery of this translational research project.

For more information please contact: jennifer.munkley@ncl.ac.uk

Information about our research groups:

https://munkleylab.co.uk/

https://www.liverpool.ac.uk/people/lu-gang-yu

Twitter: @munkleylab

Supervisor founded spin-out companies:

https://www.glycoscoredx.co.uk/

https://www.galytx.com/

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/