Last Updated: 27/05/2025
Molecular analysis of a kinase essential for replication of Plasmodium falciparum
Objectives
The goals of this project are to gain a better understanding of PfCDPK5 function and elucidate its role in parasite egress from infected erythrocytes.
- In the first aim, the localization, trafficking, and regulation of this essential kinase will be determined. Using two mass spectrometry based techniques and a third candidate gene approach.
- The experiments of the second aim will identify the in vivo substrate(s) of PfCDPK5.
Using genetic and biochemical techniques, this project will characterize the key biological process of parasite egress from red blood cells and ultimately identify new targets for future anti- malarial medications.
Malaria is the fourth leading cause of mortality for children under five years of age globally, with most of these deaths resulting from Plasmodium falciparum. A molecular understanding of the life cycle of P. falciparum will facilitate the rational design of new therapies. P. falciparum requires efficient invasion into and egress out of human erythrocytes during the asexual replication stage of the parasite life cycle. Preliminary data have identified a plant-like calcium-dependent protein kinase PfCDPK5 that is crucial for P. falciparum egress. These experiments have generated the first functional knockout of an essential blood-stage gene in P. falciparum. PfCDPK5-deficient parasites arrest at a very late-stage of the intra-erythrocytic life cycle. The hypothesis is that PfCDPK5 mediates a critical calcium-dependent signal required for P. falciparum egress.
Jul 2010 — Sep 2013
$396,900
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