A5005448992- Malaria Research and Control
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- Autophagy in Disease and Therapy
- Toxoplasma gondii Research Studies
- Drug Transport and Resistance Mechanisms
- HIV Research and Treatment
- Parasites and Host Interactions
- Ubiquitin and proteasome pathways
- Insect Resistance and Genetics
- HIV/AIDS drug development and treatment
- Phytochemical compounds biological activities
- Aquaculture disease management and microbiota
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- Plant tissue culture and regeneration
- RNA Interference and Gene Delivery
- Transgenic Plants and Applications
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Peptides and Activities
- Research on Leishmaniasis Studies
- Traditional and Medicinal Uses of Annonaceae
- Cellular transport and secretion
- Vibrio bacteria research studies
Central Drug Research Institute
2014-2024
Academy of Scientific and Innovative Research
2019-2024
Johns Hopkins University
2012-2019
New York University
2011-2012
NYU Langone Health
2009
National Botanical Research Institute
2005-2006
In response to environmental stresses, the mammalian serine threonine kinases PERK, GCN2, HRI, and PKR phosphorylate regulatory 51 of eukaryotic translation initiation factor 2α (eIF2α) inhibit global protein synthesis. Plasmodium , protozoan that causes malaria, expresses three eIF2α kinases: IK1, IK2, PK4. Like IK1 regulates stress amino acid starvation. IK2 inhibits development malaria sporozoites present in mosquito salivary glands. Here we show phosphorylation by PK4 59 is essential for...
The relict plastid (apicoplast) of the malaria parasite is site for important biochemical pathways and essential survival. sulfur mobilization ( SUF ) pathway iron–sulfur [Fe–S] cluster assembly in apicoplast Plasmodium spp. interest due to its absence human host suggesting possibility antimalarial intervention through biogenesis. We report characterization components falciparum after first step SUF. In vitro interaction experiments vivo cross‐linking showed that apicoplast‐encoded Pf SufB...
Plasmodium salivary sporozoites are the infectious form of malaria parasite and dormant inside glands Anopheles mosquitoes. During dormancy, protein translation is inhibited by kinase UIS1 that phosphorylates serine 59 in eukaryotic initiation factor 2α (eIF2α). De-phosphorylation eIF2α-P required for transformation into liver stage. In mammalian cells, de-phosphorylation mediated phosphatase 1 (PP1). Using a series genetically knockout parasites we showed sporozoites, contrary to member...
Neddylation is a type of posttranslational modification known to regulate wide range cellular processes by covalently conjugating the ubiquitin-like protein Nedd8 target proteins at lysine residues. However, role neddylation in malaria parasites has not been determined. Here, for first time, we showed that plays an essential transmission Plasmodium berghei. We found disruption did affect blood-stage propagation, gametocyte development, gamete formation, or zygote formation while abolishing...
Protozoan parasites of the genus Plasmodium cause malaria and involve infection multiple hosts cell types during life cycle. Producing sexually fit gametocytes is essential for transmitting parasite into an anopheline mosquito vector. After uptake parasites, male undergo three rounds DNA replication to produce eight nucleated flagellar gametes. Here, we report that actin-like proteins Alp5a Alp5b are involved in segregation gametogenesis. The Plasmodium-specific paralogous genes superimposed...
ABSTRACT Plasmodium parasites undergo continuous cellular renovation to adapt various environments in the vertebrate host and insect vector. In hepatocytes, berghei discards unneeded organelles for replication, such as micronemes involved invasion. Concomitantly, intrahepatic expand apicoplast that produce essential metabolites. We previously showed ATG8 conjugation system is upregulated P. liver forms (PbATG8) localizes membranes of cytoplasmic vesicles. Here, we focus on contribution...
Abstract Plasmodium sporozoites are the infective forms of malaria parasite to vertebrate host and undergo dramatic changes in their transcriptional repertoire during maturation mosquito salivary glands. We report here role a novel conserved berghei protein encoded by PBANKA_091090 Exo-erythrocytic Forms (EEFs) designate it as S porozoite surface P rotein E ssential for L iver stage D evelopment (PbSPELD). was previously annotated PB402615.00.0 its transcript recovered at maximal frequency...
The pre-erythrocytic liver stage of the malaria parasite, comprising sporozoites and stages into which they develop, remains one least understood parts lifecycle, in part owing to low numbers parasites. Nonetheless, it is recognized as an important target for antimalarial drugs vaccines. Here we provide first proteomic analysis merosomes, define final phase are responsible initiating blood infection. We identify a total 1879 parasite proteins, core set 1188 proteins quantitatively detected...
Abstract Plasmodium is an obligate intracellular parasite that requires intense lipid synthesis for membrane biogenesis and survival. One of the principal components oleic acid, which needed to maintain membrane's biophysical properties fluidity. The malaria can modify fatty acids, stearoyl‐CoA Δ9‐desaturase (Scd) enzyme catalyzes acid by desaturation stearic acid. Scd dispensable in P. falciparum blood stages; however, its role mosquito liver stages remains unknown. We show berghei...
The O-fucosylation of the thrombospondin type I repeat (TSR) domain is important for TSR-containing proteins' optimal folding and stability. However, importance Plasmodium O-fucosyltransferase 2 (POFut2) remains unclear due to two different reports. Here, we disrupted POFut2 gene in berghei demonstrated that KO parasites develop normally blood mosquito stages but show reduced infectivity mice. We found sporozoites was a diminished level TRAP affected parasite gliding motility hepatocyte...
Proteases have been implicated in a variety of developmental processes during the malaria parasite lifecycle. In particular, invasion and egress from infected hepatocyte erythrocyte, critically depend on protease activity. Although falcipain-1 was first cysteine to be characterized P. falciparum, its role lifecycle has subject some controversy. While an inhibitor blocked erythrocyte by merozoites, two independent studies showed that disruption did not affect growth blood stage parasites. To...
Abstract Plasmodium parasites have a complex life cycle that transitions between mosquito and mammalian hosts undergoes continuous cellular remodeling to adapt various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, remnant undergo extensive branching mature into hepatic merozoites. Autophagy is ubiquitous eukaryotic process permits recycling of components. Here, we show P. berghei autophagy-related E1-like...
There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia , the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes sexual multiplication. The most common type malaria caused by Plasmodium falciparum . circumsporozoite protein (CSP), major surface antigen sporozoites, protective antigen. A unique feature P. CSP its large...
Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP) throughout their life cycle. To analyze the role ICP in different cycle stages, we generated stage-specific knockout berghei (PbICP). Excision pbicb gene occurred infective sporozoites and resulted impaired sporozoite invasion hepatocytes, despite residual PbICP protein being detectable sporozoites. The vast majority these invading cultured hepatocyte cell line did not develop to mature liver but few that...
Upon entering its mammalian host, the malaria parasite productively invades two distinct cell types, that is, hepatocytes and erythrocytes during which several adhesins/invasins are thought to be involved. Many surface-located proteins containing thrombospondin Type I repeat (TSR) help establish host-parasite molecular crosstalk have been shown essential for infection. Previous reports indicated antibodies produced against Plasmodium falciparum secreted protein with altered (SPATR) block...