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Cytoskeletal dynamics in angiogenesis

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

About This PhD Project

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 elaboration 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 siRNA 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 one of our most recent discoveries – a cytoskeletal regulator that surprisingly has both cytosolic and nuclear functions. 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

References

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.

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