: Malaria is a major infectious disease. Conservative estimates predict 2-300 million people are afflicted and over a million children die from the infection each year. The growing threat of drug resistant forms of malaria has created an urgent requirement for new drugs. Targeting unique features of the parasite not found in host cells provides one approach to new drug and vaccine development. Plasmodium falciparum causes the most virulent form of human malaria. A striking feature of P. falciparum is its development in a vacuole when it infects the red cell. This host cell is non-endocytic and does not invaginate its plasma membrane. Yet P. falciparum induces both membrane invagination and vacuole formation in these cells. Thus it must exploit non-endocytic mechanisms to take up solutes and macromolecules. The long-term aim of this proposal is to identify and characterize the mechanisms by which malaria parasites develop their vacuoles for their implications on drug and toxin delivery. The studies will contribute to our understanding of the basic biology of the parasite as well as delineate mechanisms of drug resistance and vaccine delivery, and thereby contribute to human health. Molecular, genetic tools using transfection, genomics combined with high resolution imaging techniques and biochemical subcellular fractionation assays will be used to identify and purify host membrane components that are recruited into the vacuole and evaulate their associated signals required for interactions with specific lipids and protein components of both host and parasite origin that underlie vacuole formation in the infected red cell. The consequence of ablation of host or parasite gene products or expression of transdominant forms of mutant parasite genes on vacuole formation; drug and toxin uptake and parasite growth will be evaluated in in vitro cultures. These studies maybe important for understanding mechanisms of chemo and immunprophylaxis directed against a major human pathogen.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Tropical Medicine and Parasitology Study Section (TMP)
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Coyne, Philip Edward
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Northwestern University at Chicago
Schools of Medicine
United States
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Safeukui, Innocent; Gomez, NoƩ D; Adelani, Aanuoluwa A et al. (2015) Malaria induces anemia through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. MBio 6:
Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti et al. (2015) A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520:683-7
Abdul-Wahid, Badi'; Feng, Haoyun; Rajan, Dinesh et al. (2014) AWE-WQ: fast-forwarding molecular dynamics using the accelerated weighted ensemble. J Chem Inf Model 54:3033-43
Fru-Cho, Jerome; Bumah, Violet V; Safeukui, Innocent et al. (2014) Molecular typing reveals substantial Plasmodium vivax infection in asymptomatic adults in a rural area of Cameroon. Malar J 13:170
Fernandez-Pol, Sebastian; Slouka, Zdenek; Bhattacharjee, Souvik et al. (2013) A bacterial phosphatase-like enzyme of the malaria parasite Plasmodium falciparum possesses tyrosine phosphatase activity and is implicated in the regulation of band 3 dynamics during parasite invasion. Eukaryot Cell 12:1179-91
Jiang, Rays H Y; Stahelin, Robert V; Bhattacharjee, Souvik et al. (2013) Eukaryotic virulence determinants utilize phosphoinositides at the ER and host cell surface. Trends Microbiol 21:145-56
Abdul-Wahid, Badi'; Yu, Li; Rajan, Dinesh et al. (2012) Folding Proteins at 500 ns/hour with Work Queue. Proc IEEE Int Conf Escience 2012:1-8
Bhattacharjee, Souvik; Stahelin, Robert V; Speicher, Kaye D et al. (2012) Endoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell 148:201-12
Bhattacharjee, Souvik; Speicher, Kaye D; Stahelin, Robert V et al. (2012) PI(3)P-independent and -dependent pathways function together in a vacuolar translocation sequence to target malarial proteins to the host erythrocyte. Mol Biochem Parasitol 185:106-13
Marvin, Rebecca G; Wolford, Janet L; Kidd, Matthew J et al. (2012) Fluxes in ""free"" and total zinc are essential for progression of intraerythrocytic stages of Plasmodium falciparum. Chem Biol 19:731-41

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