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  The role of ubiquitin-modifying enzymes in angiogenesis


   Faculty of Biological Sciences

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The School of Molecular & Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.

We especially welcome applications that connect to the School's core research areas, which include Cancer, Cell Biology and Structural Biology. 

Higher eukaryotes display the ability to form biological tubes carrying fluids with different molecules, sugars, nutrients, lipids, and cells to tissues and organs. The vascular network is a system of interconnected blood vessels which have the capacity to arise de novo (vasculogenesis) and also sprout new blood vessels from pre-existing ones (angiogenesis). Vascular endothelial growth factors (VEGFs) bind to membrane proteins (VEGFRs) to regulate such both phenomena.

In this PhD project, we will focus on the interaction between VEGF-A and VEGFR2 which is implicated in disease states such as tumour angiogenesis. Targeting VEGFR2 activation, signalling and endothelial function is an increasingly valuable approach to blocking tumour angiogenesis, thus reducing tumour growth and metastasis. Our previous studies have highlighted a role for ubiquitination (Bruns et al., 2010; Smith et al., 2017) and de-ubiquitination (Smith et al., 2016) in controlling VEGF-A-regulated endothelial function and tubulogenesis. Ubiquitin-conjugating enzymes, ubiquitin ligases and deubiquitinases (DUBs) which target VEGFR2 are potential targets for disease therapy in cancer, heart disease and stroke. In this PhD project we build on pilot work identifying ubiquitin-conjugating enzymes (Bruns et al., 2010; Smith et al., 2017) and DUBs (Smith et al., 2016) which regulate VEGFR2 modification, turnover, signalling and angiogenesis.

The PhD student will characterise interactions between VEGFR2 and candidate ubiquitin-modifying enzymes. The role of VEGFR2-specific ubiquitin regulators will be evaluated in the context of endothelial function such as cell migration, proliferation and tubulogenesis. We will explore how targeting VEGFR2-specific regulatory enzymes can affect tumour growth and metastasis using animal models. The PhD student will be trained in biochemistry, cell biology, pharmacology and cancer biology.

Eligibility

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

  • British Council IELTS - score of 6.0 overall, with no element less than 5.5
  • TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22. 

How to apply

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable)
  • Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert

For information about the application process please contact the Faculty Admissions Team:

e:

Biological Sciences (4)

Funding Notes

This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.

References

Bruns et al. Ligand-stimulated VEGFR2 signaling is regulated by co-ordinated trafficking and proteolysis. Traffic. 2010 11:161-74.
Smith et al. (2016) VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8. Traffic. 17:53-65.
Smith et al. (2017) Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function. Biol Open. 6:1404-1415.

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