Affiliations

Professor, Microbiology, Immunology & Molecular Genetics

Member, Cell & Developmental Biology GPB Home Area

Toxoplasma gondii is an obligate intracellular parasite in the phylum Apicomplexa that causes severe central nervous system disorders of immunocompromised (AIDS/transplant/lymphoma) individuals and birth defects to congenitally infected neonates worldwide. In addition to being a globally important pathogen, Toxoplasma also serves as a model system for studying Apicomplexan parasites which cause a number of diseases of medical and veterinary importance including Plasmodium falciparum, the causative agent of malaria which kills 1-2 million people each year. Apicomplexans enter host cells by the active process of invasion that is driven by the parasite’s actin-myosin motor and involves the regulated release of the parasite’s specialized secretory organelles (the rhoptries, micronemes and dense granules). Invasion is coupled to the rhoptry-mediated formation of the parasitophorous vacuole in which the parasite resides in the cytoplasm of its host. While secretion of the rhoptries has long been implicated in the establishment of this vacuole, only a few rhoptry proteins have been reported and little is known about their precise role in this process. The Bradley lab is focusing on the role of the rhoptries in the invasion of host cells, creation of the parasitophorous vacuole in which the parasite resides, and host-parasite interaction. We have developed a method for obtaining highly purified rhoptries and analyzed this fraction using proteomic and monoclonal antibody approaches. Our proteomic analyses have identified 30 novel genes in the rhoptry fraction indicating we have identified the major proteins involved in rhoptry function. We have also produced a panel of monoclonal antibodies against the rhoptry fraction, one of which has been used to identify a rhoptry-localized protein that is targeted to the host cell nucleus, establishing a new role for the rhoptries in host-parasite interaction. Given that these proteins are present in organelles that are unique and intimately associated with infection, a complete understanding of their function promises to produce both interesting biology and important leads for ultimate control of these infections.

Dr. Bradley received his bachelor’s degree in Biology from the University of California, San Diego. At UCSD, he worked with Dr. Douglass Forbes studying the composition and function of the mammalian nuclear pore complex. He then received his PhD in Molecular Biology from UCLA in Dr. Patricia Johnson’s lab where he studied protein targeting to the hydrogenosome in the early-diverging amitochondrial eukaryote, Trichomonas vaginalis. In conjunction with phylogenetic analyses, his work on hydrogenosomal protein import was important for the conclusion that hydrogenosomes and mitochondria share a common origin. 

Dr. Bradley continued his interest in parasites and their unique organelles as a postdoctoral fellow in Dr. John Boothroyd’s lab at Stanford University studying the opportunistic pathogen Toxoplasma gondii. His research focused on the role of the secretory rhoptries in host cell invasion and host-pathogen interactions. He carried out a proteomic analysis of the rhoptries that served as a foundation for many studies that elucidated how this organelle enables the parasite to infect is human host cell, hijack host functions, and cause disease. 

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