GPCR traffic control by P-Rex Rac-GEFs

P-Rex Rac-GEFs control cell adhesion and migration through their ability to activate the small GTPase Rac. They have important roles in processes ranging from immunity and metabolism to social behaviour and are frequently deregulated in cancer, driving tumour progression and metastasis (Welch HC, 2015, Small GTPases 6:49-70).

We have data suggesting a new role of P-Rex in GPCR trafficking, independently of their ability to activate Rac. This PhD project aims to define its molecular mechanism and functional consequences.

The student will determine which steps of GPCR trafficking are affected and how, as well as P-Rex isoform and receptor specificity. S/he will evaluate the consequences for GPCR responses in cell lines and mice with altered P-Rex expression or GEF-activity. The project involves cell culture, live-cell imaging, cloning, biochemical, and cell biological methods. New research tools include constructs, cell lines and mouse strains. This project will define a novel role of a protein family that controls many physiological and disease processes.

The PhD student will be part of the Welch lab at the Babraham Institute and study at the University of Cambridge. S/he will receive additional training through the Cambridge BBSRC Doctoral Training Programme and in the lab of Andrew Massey, our industrial partner at Vernalis Research, Cambridge. This is a 4-year project starting October 2017, funded by a Cambridge BBSRC DTP iCASE studentship and Vernalis.

Please see our lab website http://www.babraham.ac.uk/our-research/signalling/heidi-welch, the Vernalis website http://www.vernalis-research.com/, or contact Heidi Welch for more information: [Email Address Removed]