The architecture of phosphoinositide signalling in vivo

Our long-term scientific interest is the analysis of cell signalling mediated by lipid molecules generated by phosphoinositide metabolism. Phosphoinositide signals provide molecular control for key sub-cellular processes such as membrane remodelling, cytoskeletal function, transcription and translation. Through these processes, this signalling pathway orchestrates basic cellular behaviours such as cell division, shape changes, polarized movement and cell death. Therefore, this pathway plays an important role in a number of physiological processes including early embryogenesis, lymphocyte development and function as well as neuronal activity. The overall goal of our work is to understand how the architecture this signalling cascade is designed to deliver optimal physiological outputs. We use Drosophila as our model system; the goal is to discover key principles of cell signalling that are likely to be conserved during evolution but are experimentally more tractable in Drosophila. It is hoped that in the medium term, our analysis in Drosophila will inform studies of equivalent signalling pathways in mammalian models with more immediate biomedical relevance.

Selected Publications:

Georgiev P, Okkenhaug H, Drews A, Wright D, Lambert S, Flick M, Carta V, Martel C, Oberwinkler J, Raghu P. (2010). TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development. Cell Metab. 12(4):386-97.

Raghu, P., Coessens, E., Manifava, M., Georgiev, P., Pettitt, T., Wood, E., Garcia-Murillas, I., Okkenhaug, H., Trivedi, D., Zhang, Q., et al. (2009). Rhabdomere biogenesis in Drosophila photoreceptors is acutely sensitive to phosphatidic acid levels. J Cell Biol 185, 129-145.

Garcia-Murillas I, Pettit T, Macdonald E, Okkenhaug H, Georgiev P, Trivedi D, Hassan B, Wakelam M and Raghu, P (2006) lazaro encodes a lipid phosphate phosphohydrolase that regulates phosphatidylinositol turnover during Drosophila phototransduction. Neuron. 29:4, 533-546.

Hardie, R.C., and Raghu, P. (2001). Visual transduction in Drosophila. Nature 413, 186-193.