The cGMP signalling pathway plays critical roles in life cycle transitions in the malaria parasite. Over the past decade we have begun to dissect the role of key players of the pathway in the human malaria parasite Plasmodium falciparum. In a recent study we have used a combination of chemical genetics and quantitative phosphoproteomics to identify several targets of the cGMP-dependent protein kinase (PfPKG). This studentship project will examine the functional significance of phosphorylation of selected PfPKG targets using genetic, cell biological and biochemical approaches.
J J Kim, C Flueck, E Franz, E Sanabria-Figueroa, E Thompson, R Lorenz, D Bertinetti, D A Baker, F W Herberg, and C Kim (2015) Crystal Structures of the Carboxyl cGMP Binding Domain of the Plasmodium falciparum cGMP-dependent Protein Kinase Reveal a Novel Capping Triad Crucial for Merozoite Egress. PloS Pathogens 11, e1004639.
M Brochet, M O Collins, T K Smith, E Thompson, S Sebastian, K Volkmann, F Schwach, L Chappell, A R Gomes, M Berriman, J C Rayner, D A Baker, J Choudhary and O Billker (2014) Phosphoinositide biosynthesis links cGMP-dependent protein kinase to essential Ca2+ signals at key decision points in the life cycle of malaria parasites. PLoS Biology 12, e1001806.
C R Collins, F Hackett, M Strath, M Penzo, C Withers-Martinez, D A Baker and M J Blackman (2013) Malaria parasite cGMP dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress. PLoS Pathogens 9, e100334.
C R Collins, S Das, EH Wong, N Andenmatten, R Stallmach, F Hackett, JP Herman, S Müller, N Meissner, MJ Blackman (2013) Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle. Molecular Microbiology 88, 687-701.
J D Dvorin, D C Martyn, S D Patel, J S Grimley, C R Collins, C S Hopp, A T Bright, S Westenberger, E Winzeler, M J Blackman, D A Baker, T J Wandless, M T Duraisingh (2010) A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science 328, 910-12.