Inflammation: Exploring the Importance of Rac-GEF Activity

P-Rex and Vav are two related protein families important for the recruitment of white blood cells to sites of infection during the inflammatory response. They are GEF proteins that activate the small GTPase Rac, and this catalytic Rac-GEF activity is crucial for most of their functions. In leukocytes, individual GEF proteins from both families, P-Rex1 and Vav1, cooperate in the activation of Rac and of Rac-dependent cell responses. However, Vav1 can also signal independently of its Rac-GEF activity, and preliminary evidence suggests that P-Rex1 also has GEF-activity independent roles. The objective of this studentship is to assess the importance of the P-Rex1 and Vav1 Rac-GEF activities for leukocyte recruitment during inflammation and for the ability of leukocytes to clear infections.
The PhD student will determine the effects of P-Rex1 and Vav1 expression and their Rac-GEF activities on leukocyte recruitment during inflammation and infection. S/he will learn to analyse Rac-GEF signalling pathway activity, generate genetically-modified mouse strains, assess leukocyte host defence responses in isolated cells and in vivo, and become an expert in small GTPase and related pathways and in the mechanisms regulating inflammation and host defence.