Functional analysis of the downstream mediators of cyclic nucleotide signalling in malaria parasites

Malaria parasites replicate asexually in the bloodstream of patients, causing all the symptoms of disease. Parasite proliferation also generates male and female parasites, which are taken up by a feeding mosquito and have sex in the mosquito to allow disease transmission. A parasite biochemical pathway called cyclic nucleotide signalling controls critical steps in the progression of this complex malarial life cycle. Using genetic and biochemical approaches we have discovered which malaria parasite enzymes (cyclases, phosphodiesterases and protein kinases) in this pathway are important for asexual and sexual development. We have also identified a novel protein which is key to the link between cyclic nucleotide signalling with another essential pathway driven by cellular calcium. We now want to determine the detailed mechanisms by which these proteins and pathways interact, and importantly how we can disrupt the pathways to provide targets and a rational framework for the development of next-generation antimalarial drugs.