Investigation of the role of protein phosphorylation in the erythrocytic stage of the human malarial parasite Plasmodium falciparum. (360G-Wellcome-090313_Z_09_Z)

This project is divided into three objectives: 1. To determine the global phospho-proteome in the schizont stage of P. falciparum. 2. To establish the phosphorylation networks regulated by specific protein kinases that are essential for parasite viability. 3. To determine the role of phosphorylation in parasite growth and invasion into red blood cells. Meeting these objectives is centred on the integration of three core approaches. The first is the application of biochemical/mass spectro metry techniques that will define the phospho-proteome of P. falciparum. The second is the use of a novel chemical genetics approach in combination with pharmacological inhibitors to inhibit specific protein kinases and thereby probe the molecular mechanisms by which phosphorylation contributes to parasite viability. Thirdly, the phosphorylation events discovered in this project will be set in a functional context by studying progression of the parasite through the erythrocytic cycle and parasit e invasion into erythrocytes. By combining these three approaches we aim to both further our basic understanding of the role played by phosphorylation in P. falciparum but also to contribute to the protein kinase based drug discovery programme being conducted in the Doerig lab (co-applicant).