New molecules and mechanisms 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 2025/26. This opportunity is open to candidates who have the means to self-fund their studies or who have a PhD sponsor who will cover this cost. We especially welcome applications that connect to the School's core research areas, which include Cancer, Cell Biology and Structural Biology.

<p>Multicellular eukaryote organisms from fish to man have the inherent ability to form biological tubes which transport fluids, proteins, sugars, lipids, and cells to different tissues and organs. The blood vessel or vascular network is a system of interconnected biological tubes which arises de novo (vasculogenesis) and via sprouting (angiogenesis). Vascular endothelial growth factor (VEGF) binding to membrane proteins with receptor tyrosine kinase activity (VEGFRs) regulates vasculogenesis and angiogenesis. We still do not understand how the endothelial cell integrates signalling, trafficking, VEGFR turnover and gene expression to control angiogenesis. This project will test the hypothesis that VEGFR-VEGF activation and downstream signalling is dependent on specific interactions in a time (temporal) and location (spatial) dependent manner. Better understanding of such events will allow us to better manipulate VEGF-dependent angiogenesis in cancer, heart disease and some forms of blindness. Our previous studies have highlighted a role for ubiquitination (Smith et al., 2017; Critchley et al., 2023) and de-ubiquitination (Smith et al., 2016) in controlling VEGF-A-regulated endothelial function and tubulogenesis. We are also exploring the use of synthetic proteins and small molecules to target membrane proteins and ubiquitin-modifying enzymes in endothelial function and disease states (Roper et al., 2023; Zhu et al., 2025).</p> <p>The PhD project will undertake detailed studies of the interactions between VEGFRs, membrane-bound and soluble factors which influence signal transduction and endothelial function exploring effects on cell migration, proliferation and angiogenesis. The PhD student will be trained in biophysics, bioinformatics, structural biology, biochemistry, cancer biology and vascular physiology.</p> <h5>References</h5> <ul> <li>Critchley et al. (2023) The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function. J Cell Sci. 2023 136:jcs260657.</li> <li>Hall et al. (2025) Modified Lipid Particle Recognition: A Link Between Atherosclerosis and Cancer? Biology 14:675.</li> <li>Roper et al. (2023) "Affimer" synthetic protein scaffolds block oxidized LDL binding to the LOX-1 scavenger receptor and inhibit ERK1/2 activation. J Biol Chem. 299:105325.</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.</li> <li>Zhu et al. (2025) Structure and function of MDM2 and MDM4 in health and disease. Biochem J. 482:BCJ20240757.</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.

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>