The role of ubiquitin-modifying enzymes in angiogenesis

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

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

<p>To apply for this project opportunity applicants should complete an <a href="https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply">online application form</a> and attach the following documentation to support their application. </p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks</li> <li>Evidence that you meet the University's minimum English language requirements (if applicable)</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Biological Sciences as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul> <p>If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below).</p> <p><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p>

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. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<p>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. </p> <p> </p>

<p>For information about the application process please contact the Faculty Admissions Team:</p> <p>e: <a href="mailto:fbsgrad@leeds.ac.uk">fbsgrad@leeds.ac.uk</a></p>