The aim of the proposed project is a characterization of a set of unique and understudied kinases that have essential functions in Apicomplexan life cycle control. These kinases, which interestingly are only found in plants and protists and not in animals or fungi, are calcium-dependent and are thought to allow for a translation of intra- or extracellular Ca2+ signals into an appropriate cellular response. The specific objectives of this proposal are (1) functional studies of two Plasmodium calcium-dependent protein kinases (CDPK1 and CDPK5) to elucidate their regulatory role in the Plasmodium life cycle, and (2) to validate these proteins as essential signaling molecules that can serve as drug targets in an attempt to effectively treat Plasmodium infection/malaria. Our proposed studies involve the construction of transgenic parasites that express epitope-tagged copies of CDPK1 and CDPK5, as well as state-of-the-art conditional knock-out and chemical genetics approaches to investigate the biological function of these proteins. In addition, a collaboration with the biophysics laboratory of Professor Jane Endicott at the University of Oxford is proposed, to produce crystallized protein for structural analysis.
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