A5060108187- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- interferon and immune responses
- Aquaculture disease management and microbiota
- Parasitic Infections and Diagnostics
- Inflammasome and immune disorders
- Rabies epidemiology and control
- Heme Oxygenase-1 and Carbon Monoxide
- Mosquito-borne diseases and control
- Trypanosoma species research and implications
- Immune Response and Inflammation
- Invertebrate Immune Response Mechanisms
- Immune cells in cancer
- Aquaculture Nutrition and Growth
- Autophagy in Disease and Therapy
- Parasite Biology and Host Interactions
- Nitric Oxide and Endothelin Effects
- RNA Interference and Gene Delivery
- Yersinia bacterium, plague, ectoparasites research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Viral Infections and Vectors
- RNA Research and Splicing
University of California, Davis
2016-2025
Massachusetts Institute of Technology
2009-2020
IIT@MIT
2009-2015
Stanford University
2005-2011
Washington University in St. Louis
2006
University of Cambridge
2006
Wageningen University & Research
1998-2005
Bipar
2003
The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify responsible genes, we mapped virulence F 1 progeny derived crosses between type II III strains, which introduced into mice. Five ( VIR ) loci were thus identified, for two these, genetic complementation showed a predicted protein kinase (ROP18 ROP16, respectively) is key molecule. Both are hypervariable...
NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate pathway, parasite-derived effectors involved are unknown. We determined type II strains activate more than I or III strains, and using forward genetics we found this difference a result polymorphic protein GRA15, novel dense granule which secretes into host cell upon invasion. A GRA15-deficient strain has severe defect in both nuclear translocation...
Induction of immunity that limits Toxoplasma gondii infection in mice is critically dependent on the activation innate immune response. In this study, we investigated role cytoplasmic nucleotide-binding domain and leucine-rich repeat containing a pyrin (NLRP) inflammasome sensors during acute toxoplasmosis mice. We show vitro murine bone marrow-derived macrophages activates NLRP3 inflammasome, resulting rapid production cleavage interleukin-1β (IL-1β), with no measurable IL-18 pyroptosis....
Toxoplasma gondii , an obligate intracellular parasite of the phylum Apicomplexa, has unusual ability to infect virtually any warm-blooded animal. It is extraordinarily successful parasite, infecting estimated 30% humans worldwide. The outcome infection highly dependent on allelic differences in large number effectors that secretes into host cell. Here, we show largest determinant virulence difference between two most common strains ROP5 locus. This segment genome consisting a family 4–10...
Abstract Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals causing zoonotic infections in humans. T. differs substantially its broad distribution from closely related that typically have narrow, specialized host ranges. To elucidate genetic basis for these differences, we compared genomes of 62 globally distributed isolates to several coccidian parasites. Our findings reveal tandem amplification diversification secretory pathogenesis...
The obligate intracellular parasite Toxoplasma gondii secretes effector proteins into the host cell that manipulate immune response allowing it to establish a chronic infection. Crosses between types I, II and III strains, which are prevalent in North America Europe, have identified several secreted effectors determine strain differences mouse virulence. polymorphic rhoptry protein kinase ROP18 was recently shown difference virulence type I strains by phosphorylating inactivating...
We examined the in vivo growth, dissemination, and reactivation of strains protozoan parasite Toxoplasma gondii using a bioluminescence-based imaging system. Two T. strains, one with highly virulent disease phenotype mice (S23) other 1,000-fold-lower virulence (S22), were engineered to stably express light-emitting protein luciferase. One clone each wild-type strain was isolated, two clones (S23-luc7 S22-luc2) found similar levels Mice infected intraperitoneally S23-luc7 (50 or 5 parasites)...
Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring resistance rats was previously mapped region chromosome 10 containing Nlrp1. This gene encodes inflammasome sensor controlling macrophage sensitivity anthrax lethal toxin (LT) induced rapid cell death (pyroptosis). We show here rat strain differences infected pyroptosis, IL-1β/IL-18 processing, and inhibition...
IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed IFN-γ-dependent re-localization mGBP1 to parasitophorous vacuole (PV) correlates virulence type parasite. identified three parasitic factors, ROP16, ROP18, GRA15 determine strain-specific accumulation on PV. These highly...
Most isolates of Toxoplasma from Europe and North America fall into one three genetically distinct clonal lineages, the type I, II III lineages. However, in South these strains are rarely isolated instead a great variety other found. T. gondii differ widely number phenotypes mice, such as virulence, persistence, oral infectivity, migratory capacity, induction cytokine expression modulation host gene expression. The outcome toxoplasmosis patients is also variable we hypothesize that, besides...
Abstract Macrophages play an essential role in the early immune response against Toxoplasma and are cell type preferentially infected by parasite vivo. Interferon gamma (IFNγ) elicits a variety of anti- activities macrophages. Using genome-wide CRISPR screen we identify 353 genes that determine fitness naїve or IFNγ-activated murine macrophages, seven which further confirmed. We show one these encodes dense granule protein GRA45, has chaperone-like domain, is critical for correct...
Toxoplasma infection causes serious complications in immunocompromised individuals and the developing fetus. During infection, certain immune cells release a protein called interferon gamma that activates to destroy parasite or inhibit its growth.