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Cytoskeletal dynamics and intracellular trafficking in angiogenesis

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Angiogenesis is the fundamental physiological process by which new blood vessels are generated from pre-existing vasculature. It plays a critical role in formation of the vasculature during development; however, this process is also triggered in hypoxic tissue in the adult organism – for example, in response to myocardial infarction or stroke. This neovascularisation plays an important role in healing and regeneration. In addition to its positive roles in tissue healing, angiogenesis is also triggered in several disease states. In cancer, solid tumors secrete angiogenic factors that force the body to create a new blood supply for the tumor, supporting its growth and metastasis. Because of the importance of angiogenesis in health and disease, major efforts have been focused on understanding the processes that control it. Understanding the mechanisms of angiogenesis is critical for the development of new drugs for the clinical control of blood vessel formation.

My laboratory is focussed on understanding how cytoskeletal regulators control the formation of blood vessels – a fundamental process in biology. By using a combination of gene screening and advanced proteomics, we have managed to identify a host of novel signalling proteins involved in cytoskeletal regulation of this process. This project seeks to understand the mechanisms of blood vessel formation, and to identify novel drug targets for its clinical manipulation.

The studentship will involve training in the key techniques of cytoskeletal research, including cell migration assays, proteomics and advanced cell imaging. The project will make heavy use of the Wolfson Bioimaging Facility – one of the leading centres for microscopy in the UK. Outcomes of the project will have direct relevance for the clinical manipulation of angiogenesis; however, the study will also have broader relevance for cytoskeletal regulation in other systems.

The student will join a dynamic, international research group situated in the School of Biochemistry. Bristol is a centre for cytoskeletal research, and the student will benefit from exposure to a wide range of exciting work in this area. The city is exciting, cosmopolitan and culturally diverse, with good flight connections to European cities.

Webpages:
http://www.bris.ac.uk/biochemistry/people/harry-h-mellor/overview.html

Funding Notes

If you are an Overseas Student with your own funding, please email Professor Mellor directly using the form below.

If you are a UK student, you can access this project by applying to the University of Bristol Welcome Trust Dynamic Cell PhD program, or the University of Bristol BHF PhD program in Integrative Cardiovascular Science.

References

Gurevich D, Severn C, Twomey C, Greenhough A, Cash J, Toye A, Mellor H, Martin P (2018) Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression EMBO J. DOI: 10.15252/embj.201797786

Richards M, Hetheridge C and Mellor H (2015) The formin FMNL3 controls early apical specification in endothelial cells by regulating the polarized trafficking of podocalyxin. Current Biology 27, 2325-2331.

Hetheridge C, Scott AN, Swain RK, Copeland JW, Higgs HH, Bicknell R and Mellor H. (2012) The novel formin FMNL3 is a cytoskeletal regulator of angiogenesis. J Cell Sci. 125, 1420-1428.

Potente M, Gerhardt H, Carmeliet P. (2011) Basic and therapeutic aspects of angiogenesis. Cell 16, 873-87.

How good is research at University of Bristol in Biological Sciences?

FTE Category A staff submitted: 64.60

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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