BILLKER, OLIVER · Molecular mechanisms regulating gamete formation in malaria parasites

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Project objective

Transmission of malaria parasites to the mosquito vector is initiated inside the blood meal by the rapid differentiation of gametocytes into gametes. Game to genesis is an explosive event that is strictly regulated by extracellular stimuli. At a permissive temperature game to genesis is triggered within seconds by a small mosquito molecule, xanthurenic acid (XA). The rapid and highly synchronised differentiation response of malarial gametocytes to a defined molecular trigger now offers a unique model to study molecular mechanisms of signal transduction and cellular regulation in Plasmodium. In a discovery-based strategy for the identification of key regulators of game to genesis, the proposed project will use functional proteomics to identify those proteins in P.falciparum gametocytes that are specifically modified in response to XA by (de)phosphorylation, proteolytic processing or other secondary modifications. Candidate proteins will be examined for their role in malaria transmission by targeted gene disruption in P. berghei.Insights will be gained into the role of tyrosine vs. serine/threonine phosphorylation in Plasmodium, and key kinase substrates will be identified. These may include a hypothetical XA receptor, autophosphorylating kinases, and regulators of the cell cycle or proteolytically processed proteins of parasite of host erythrocyte. The proposed project will provide basic insights into signal transduction in Plasmodium and may reveal new targets for pharmacological intervention that would not necessarily be limited to sexual stages. Furthermore, this project will make a unique contribution to the annotation of the P.falciparum genome.

Original text from CORDIS.

Participants

• IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE · LONDONCoordinatorUnited Kingdom

Links

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