Malaria parasites are obligatory intracellular protists in the genus Plasmodium that are transmitted by Anopheline mosquitoes; continuously cycling their residence between their insect vectors and mammalian hosts where they undergo extensive growth and development. The exo-erythrocytic stage of a Plasmodium infection is an attractive interventional target since few parasites are present in the host, clinical symptoms are absent and it results in a massive parasite amplification event, releasing tens of thousands of intra-erythrocytic stage parasites that will go on to cause symptomatic disease. Despite the fact that exo-erythrocytic development (schizogony) is a critical parasite amplification event, little is known about the molecular factors that control this unique form of replication.
My research lab examines the morphological changes that occur on the parasite plasma membrane (PPM) during the mosquito- to liver-stage transition, providing a more comprehensive understanding of the infection-related proteins that initiate exo-erythrocytic development by examining the role of multi-protein complexes at the PPM. Recent investigations into differential gene expression patterns in Plasmodium oocyst- and salivary gland-derived sporozoites lead to the identification of the Plasmodium BEM46-like protein (PBLP), which is contained within intracellular vesicles that are translocated to the PPM during sporozoite differentiation in infected hepatocytes. All eukaryotic organisms carry a homologue of the bud emergence (BEM)46 protein, which possesses a conserved amino acid motif of the α/β-hydrolase superfamily, though few have known biological functions despite being implicated in signal transduction pathways that affect cell morphogenesis.
Current projects include:
1. Characterization of the functional role of the catalytic domain of PBLP in parasite invasive-stage membrane morphogenesis during the mosquito- to liver-stage transition using a combination of biochemical approaches.
2. Investigation of the molecular mechanisms underlying the unique cell morphogenesis of Plasmodium parasites during early liver-stage development.
3. Examination of the protein interactive network on the Plasmodium parasite plasma membrane during the mosquito- to liver-stage transition.
4. Examination of age-dependent maturation as it pertains to sporozoite infectivity in Anopheles stephensi mosquitoes.
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