New molecules and mechanisms in angiogenesis

Summary

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. 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.

Multicellular eukaryote species ranging from fish to man can form biological tubes which transport fluids, proteins, sugars, lipids, and cells to tissues and organs. The network of blood vessels (vasculature) is one such system of interconnected biological tubes which arises de novo (vasculogenesis) and via sprouting (angiogenesis). Vascular endothelial growth factor (VEGF) binding to membrane proteins (VEGFRs) regulates such phenomena. A PhD project within the Endothelial Cell Biology Unit will be supervised by basic and clinical scientists and focus on the interactions between VEGF-A with VEGFR1 and VEGFR2 which regulate signaling, trafficking, turnover and angiogenesis. Understanding the link between VEGFR-VEGF signaling, trafficking and turnover impacts on our ability to intervene in angiogenesis in diseases such as cancer, heart disease and some forms of blindness. Our previous studies have highlighted a role for ubiquitination (Bruns et al., 2010; Smith et al., 2017; Critchley et al., 2023) and de-ubiquitination (Smith et al., 2016) in controlling VEGF-A-regulated endothelial function and tubulogenesis. Ubiquitin-modifying enzymes, ubiquitin ligases and deubiquitinases (DUBs) which target VEGFR2 are potential targets for disease therapy in cancer, heart disease and stroke.

The PhD project will undertake detailed studies of the interactions between VEGFR2, ubiquitin-modifying enzymes, membrane-bound and soluble factors. The role of tyrosine kinase activity and substrate binding will be studied in the context of endothelial function such as cell migration, proliferation and angiogenesis. The PhD student will be trained in biophysics, bioinformatics, structural biology, biochemistry, cancer biology and vascular physiology.

References

• Bruns et al. Ligand-stimulated VEGFR2 signaling is regulated by co-ordinated trafficking and proteolysis. Traffic. 2010 11:161-74.
• Critchley et al. The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function. J Cell Sci. 2023 136:jcs260657.
• 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.

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.