Oxygen sensing. (360G-Wellcome-096956_Z_11_Z)

My overarching questions are 1) How do different cells and organisms adapt to changes in oxygenation? 2) Can we use knowledge of molecular oxygen sensing pathways to understand and treat disease processes? The specific questions that I plan to focus on in the short-to-medium term are: 1) What are the effects of inactivating the von Hippel Lindau (VHL) tumour suppressor and of activating Hypoxia-Inducible Factor (HIF) in B lymphocytes? Is there a pathway capable of efficiently degradi ng HIF alpha which is independent of VHL in B lymphocytes. If such a pathway exists, how does it operate? 2) Following VHL loss of function, what are the key steps which lead to tumour formation? At different stages on the path to tumour formation is it possible to selectively kill cells that lack VHL? 3) Which prolyl hydroxylase(s) are responsible for hydroxylating components of the complement C1q complex, and other molecules besides HIF alpha subunits and collagen.