Plasmodium Cynomolgi
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ABSTRACT:
PROVIDER: PRJNA356968 | ENA |
REPOSITORIES: ENA
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Project description:Malaria sporozoites, the form transmitted by mosquitoes, are quiescent while in the insect salivary glands. It is only after the sporozoites are deposited in the host’s skin, migrate to the liver and infect hepatocytes that the parasites continue the life cycle. We show that the sporozoite latency is an active process that requires phosphorylation of the eukaryotic initiation factor-2α (eIF2α) by a sporozoite-specific kinase. Inactivation of the kinase gene leads to an overall enhancement of protein synthesis including of silenced liver stage proteins, and inhibits transmission of malaria. Specific inhibition of the eIF2α phosphatase by salubrinal has the opposite effect. Thus, to prevent premature transformation into liver stages, Plasmodium sporozoites exploit the same mechanism that regulates stress responses in mammalian cells.
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Project description:Malaria sporozoites, the form transmitted by mosquitoes, are quiescent while in the insect salivary glands. It is only after the sporozoites are deposited in the hostâs skin, migrate to the liver and infect hepatocytes that the parasites continue the life cycle. We show that the sporozoite latency is an active process that requires phosphorylation of the eukaryotic initiation factor-2α (eIF2α) by a sporozoite-specific kinase. Inactivation of the kinase gene leads to an overall enhancement of protein synthesis including of silenced liver stage proteins, and inhibits transmission of malaria. Specific inhibition of the eIF2α phosphatase by salubrinal has the opposite effect. Thus, to prevent premature transformation into liver stages, Plasmodium sporozoites exploit the same mechanism that regulates stress responses in mammalian cells. 4 samples overall, 2 wt and 2 KO (PbeIK2 knockout) samples
2010-05-16 | E-GEOD-16259 | biostudies-arrayexpress
Project description:A major obstacle in deciphering the hepatic stage of the malaria parasite has been the challenges associated with culturing the infected hepatocytes through the entire liver stage cycle, including that of the dormant form known as hypnozoites. Primary hepatocytes lose their specialized functions in long-term in vitro culture. Hepatocyte infection represents the first step for clinically silent infection and development of malaria parasite Plasmodium in the liver. Thus this liver stage is an ideal target for development of novel antimalarial drugs and vaccine. However, drug discovery against Plasmodium liver stage is severely hampered by the poor understanding of host-cell and parasites interactions during the liver stage infection and development. In this study, we have performed tandem mass tags (TMT) labelling based quantitative proteomic analysis in simian primary hepatocytes cultured in three different systems of susceptibility to plasmodium infection. Our results represent the first documentation of potentially essential molecular markers including asialoglycoprotein receptor (ASGPR), apolipoproteins, squalene synthase and scavenger receptor B1 (SR-BI) required for productive infection and full development in relapsing Plasmodium species. The identification of these candidate proteins for constructive infection and development of Plasmodium in malaria paves the way to explore them as therapeutic targets.
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Project description:Most malaria drug development focuses on parasite stages detected in red-blood cells even though to achieve eradication next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4,000 commercially available compounds with previously demonstrated blood stage activity (IC50 < 1 µM), and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. Our orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 mg/kg) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.
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Project description:This experiment characterizes the localisation of H2A.Z, H3K9ac and H3K4me3 in the epigenome of the human malaria parasite, P. falciparum at 4 different stages of intraerythrocytic development. Examination of H2A.Z, H3K9ac, H3K4me3 and mono-nucleosomal input in 3D7 strain at 4 different stages and H2A in 3D7 strain at 1 stage using native ChIP-seq
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Project description:This experiment characterizes the localisation of H2A.Z, H3K9ac and H3K4me3 in the epigenome of the human malaria parasite, P. falciparum at 4 different stages of intraerythrocytic development.
2010-10-28 | GSE23867 | GEO