Proteins rarely work in isolation and often form physical complexes that are critical for their activity. Defining these interactions is key to understanding biological function. This project focusses on the two-pore channel which is a recently identified intracellular ion channel which regulates cytosolic Ca2+ ion concentrations. The aim is to use computational approaches incorporating evolutionary information to define the TPC “interactome” and use molecular techniques to validate novel interactions. Coupling both “dry” and “wet” approaches will provide novel insight into a family of contemporary significance.
Brailoiu, E., Churamani, D., Cai, X., Schrlau, M. G., Brailoiu, G. C., Gao, X., Hooper, R., Boulware, M. J., Dun, N. J., Marchant, J. S. and Patel, S. (2009) Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. J.Cell Biol. 186, 201-209
Cai, X. and Patel, S. (2010) Degeneration of an intracellular ion channel in the primate lineage by relaxation of selective constraints. Mol.Biol.Evol. 27, 2352-2359
Patel, S., Marchant, J. S. and Brailoiu, E. (2010) Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals. Cell Calcium 47, 480-490
Ranea, JA, Reid, A, Yeats, C & Orengo, CA (2010) Study of the Dark Matter in Protein Network Prediction and Modelling. PLoS Comp. Biol, 6, pii: e1000945.
Lees J, Yeats C, Perkins J, Sillitoe I, Rentzsch R, Dessailly B.H, Orengo C. (2012) Gene3D: a domain-based resource for comparative genomics, functional annotation and protein network analysis. Nucleic Acids Res. 40:465-71.