A5002955450- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Parasitic Infections and Diagnostics
- Cytomegalovirus and herpesvirus research
- Malaria Research and Control
- Mosquito-borne diseases and control
- Bacteriophages and microbial interactions
- Rabies epidemiology and control
- Autophagy in Disease and Therapy
- Trypanosoma species research and implications
- Calpain Protease Function and Regulation
- Coccidia and coccidiosis research
- Venomous Animal Envenomation and Studies
- Protist diversity and phylogeny
- Aquaculture disease management and microbiota
- HIV Research and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- interferon and immune responses
- Vector-borne infectious diseases
- Research on Leishmaniasis Studies
- Cellular transport and secretion
University of Geneva
2016-2025
Cyclerion (United States)
2019
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019
University of Kassel
2019
Swiss National Science Foundation
2019
University of Helsinki
2019
European Research Council
2019
London School of Hygiene & Tropical Medicine
2019
École Polytechnique Fédérale de Lausanne
2013
Carnegie Mellon University
2012
A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy malaria. This includes 1-deoxy- d -xylulose 5-phosphate (DOXP) as a key metabolite. The presence two genes encoding the enzymes DOXP synthase and reductoisomerase suggests that P. depends on pathway. is probably located apicoplast. recombinant inhibited by fosmidomycin its derivative, FR-900098. Both drugs suppressed vitro growth...
Myosins are eukaryotic actin-dependent molecular motors important for a broad range of functions like muscle contraction, vision, hearing, cell motility, and host invasion apicomplexan parasites. Myosin heavy chains consist distinct head, neck, tail domains have previously been categorized into 18 different classes based on phylogenetic analysis their conserved heads. Here we describe comprehensive examination many unclassified myosins, with particular emphasis sequences from other...
Obligate intracellular apicomplexan parasites rely on gliding motion powered by their actomyosin system to disperse throughout tissues and penetrate host cells. Toxoplasma gondii myosin A has been implicated in this process, but direct proof lacking. We designed a genetic screen generate tetracycline-inducible transactivator T. gondii. The MyoA gene was disrupted the presence of second regulatable copy MyoA. Conditional removal caused severe impairment cell invasion parasite spreading...
Malaria is caused by unicellular Plasmodium parasites. relies on diverse microtubule cytoskeletal structures for its reproduction, multiplication, and dissemination. Due to the small size of this parasite, cytoskeleton has been primarily observable electron microscopy (EM). Here, we demonstrate that nanoscale organisation within reach using ultrastructure expansion (U-ExM). In developing microgametocytes, U-ExM allows monitoring dynamic assembly axonemes concomitant tubulin polyglutamylation...
Expansion microscopy (ExM) is a highly effective technique for super-resolution fluorescence that enables imaging of biological samples beyond the diffraction limit with conventional microscopes. Despite development several enhanced protocols, ExM has not yet demonstrated ability to achieve precision nanoscopy techniques such as Single Molecule Localization Microscopy (SMLM). Here, address this limitation, we have developed an iterative ultrastructure expansion (iU-ExM) approach achieves...
Toxoplasma gondii is a protozoan pathogen that produces severe disease in humans and animals. This obligate intracellular parasite provides an excellent model for the study of how such pathogens are able to invade, survive, replicate intracellularly. DNA encoding chloramphenicol acetyltransferase was introduced into T. transiently expressed with use three vectors based on different genes. The ability introduce genes have them efficiently faithfully essential tool understanding...
A system for stable transformation of Toxoplasma gondii tachyzoites was developed that exploited the susceptibility to chloramphenicol. Introduction chloramphenicol acetyltransferase (CAT) gene fused flanking sequences followed by selection resulted in parasites stably expressing CAT. construct incorporating tandemly repeated gene, B1 , targeted efficiently its homologous chromosomal locus. Knockout single-copy ROP1 also successful. Stable should permit identification and analysis genes...
Toxoplasma gondii is an obligate intracellular parasite and important human pathogen. Relatively little known about the proteins that orchestrate host cell invasion by T. or related apicomplexan parasites (including Plasmodium spp., which cause malaria), due to difficulty of studying essential genes in these organisms. We have used a recently developed regulatable promoter create conditional knockout apical membrane antigen-1 (TgAMA1). TgAMA1 transmembrane protein localizes parasite's...
Infection by Toxoplasma gondii down-regulates the host innate immune responses, such as proinflammatory cytokine production, in a Stat3-dependent manner. A forward genetic approach recently demonstrated that type II strain fails to suppress responses because of potential defect highly polymorphic parasite-derived kinase, ROP16. We generated ROP16-deficient I parasites reverse genetics and found severe parasite-induced Stat3 activation, culminating enhanced production interleukin (IL) 6 IL-12...
The intracellular protozoan parasite Toxoplasma gondii shares with other members of the Apicomplexa a common set apical structures involved in host cell invasion. Micronemes are secretory organelles releasing their contents upon contact cells. We have identified transmembrane micronemal protein MIC6, which functions as an escorter for accurate targeting two soluble proteins MIC1 and MIC4 to micronemes. Disruption MIC1, MIC4, MIC6 genes allowed us precisely dissect contribution sorting...
Regulated exocytosis by secretory organelles is important for malaria parasite invasion and egress. Many effector proteins, including perforins, adhesins, proteases, are extensively proteolytically processed both pre- postexocytosis. Here we report the multistage antiplasmodial activity of aspartic protease inhibitor hydroxyl-ethyl-amine-based scaffold compound 49c. This inhibits preexocytosis processing several secreted rhoptry microneme proteins targeting corresponding maturases...
Toxoplasma gondii , as an obligate intracellular and promiscuous pathogen of mammalian cells, utilizes host sugars for energy to generate glycoconjugates that are important its survival virulence. Here, we report T. glucose transporter (TgGT1) is proficient in transporting mannose, galactose, fructose besides glucose, serves a major hexose at plasma membrane. harbors 3 additional putative sugar transporters (TgST1–3), which TgST2 expressed surface, whereas TgST1 TgST3 intracellular....
While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these lack mitochondrial isoform of pyruvate dehydrogenase identity enzyme catalyses conversion acetyl-CoA remains enigmatic. Here we demonstrate branched chain ketoacid (BCKDH) complex is missing link, functionally replacing PDH both T. P. berghei....
The ROP18 kinase has been identified as a key virulence determinant conferring high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into host cells during invasion; however, molecular mechanisms which this exerts its pathogenic action remain poorly understood. In study, we show that targets endoplasmic reticulum-bound transcription factor ATF6β. Disruption gene severely impairs acute toxoplasmosis RH strain....