PhD in Cell Biology – The role of heparan sulphate proteoglycans in exosome-mediated growth factor delivery & prostate tumour growth

  • ORGANISATION/COMPANY – Cardiff University
  • RESEARCH FIELD – Biological sciences – Medical sciences
  • RESEARCHER PROFILE – First Stage Researcher (R1)
  • APPLICATION DEADLINE – 28/02/2017 17:00 – Europe/London

This is a full time, 3-year, PhD project funded by Cancer Research Wales, and will be completed within our Division of Cancer and Genetics.

The proposal shall involve in depth analysis of prostate cancer exosomes, growth factor signalling mechanisms, and 3D cell culture systems. Collectively, the experienced supervisors will deliver a unique training experience, providing expertise in expertise in biological assays, data analysis and critical review. All of which are highly transferable to other disciplines.

The project

In patients with prostate cancer, stromal cells surrounding the stroma become abnormally activated and become myofibroblast-like. The exact origin of these myofibroblasts is unclear, but we have previously implicated nanometre-sized vesicles, termed exosomes, in the delivery of growth factors (such as TGFbeta) leading to stromal cell differentiation. TGFbeta alone, however, is not sufficient to generate these disease-associated stromal cells, suggesting simultaneous delivery of multiple factors may be required.

We have recently shown that prostate cancer exosomes express a variety of heparan sulphate proteoglycans (HSPGs) on their surface. HSPGs are known to bind to a variety of growth factors. We therefore hypothesis that removal of HSPGs will alter the repertoire of growth factors on the exosome surface and in turn change the function of exosomes.

The project will utilise proteome profiling to determine the growth factors tethered to the exosome surface via HSPGs. This shall involve the use of exosomes with altered HSPG profiles, from cell lines generated by us.

Multiple techniques will be used to explore the role of HSPGs in regulating exosome function, and use of 3D cell culture models will enable us to determine the role of exosomal HSPGs in regulating tumour growth. The project has implications for basic mechanisms of disease, but also has translational elements involving the use of exosomes as a source of disease biomarkers.

The Division of Cancer and Genetics

The division is one of four research divisions within the School of Medicine. It has approximately 170 staff and 70 postgraduate research students, housed across multiple research buildings all within close proximity on the Heath Park Campus.

Researchers within the division also have strong collaborative links with researchers throughout the university and local NHS Trusts.

There is also an annual division postgraduate research day, organised by research students, providing an ideal opportunity for students to showcase their work. There are also numerous social events organised throughout the year.

Training environment

The School of Medicine has an excellent training programme whereby all students undergo a one week course as part of their induction.

Students also have access to a wide selection of courses on research skills, through the Doctoral Academy.

The School of Medicine was ranked in the top 10 of UK Medical Schools in REF2014. There is high student satisfaction with 90% of students being satisfied with their research environment.

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