- B.S., State University of Utrecht, 1982
- Ph.D., Yale University, 1989
- Princeton University, 1989-90
- Mem. Sloan Kettering Cancer Center, 1990-91
- National Institutes of Health
The research in my laboratory revolves around the human protozoan parasite Toxoplasma gondii. This organism can cause severe disease in individuals with a defective immune system or during pregnancy. In addition, it is also used as a model system for study of the closely related malaria parasite, Plasmodium. Both organisms are obligate intracellular parasites of animals and have evolved numerous unique regulatory and structural elements to penetrate and survive inside animal cells. We are concentrating our efforts on two general areas of Toxoplasma gondii cell biology: essential signaling pathways in the parasite and the structure, assembly, and function of its membrane skeleton.
First, we are analyzing the signaling pathways that govern Toxoplasma behavior during an essential aspect of its life cycle: the escape from a dying host cell and the attachment to and invasion into a new host cell.
We have previously determined that specifically the loss of potassium from a dying or disrupted host cell triggers an increase in cytoplasmic calcium in the parasite. The resulting activation of several calcium-dependent effectors then activates parasite motility and escape from the host cell. Currently we are analyzing the mechanisms in the parasite that sense the host cell environment and control the parasites’ cytoplasmic calcium levels. In addition, we are analyzing the exact role of a calcium-dependent protein kinase that is essential in the activation of parasite motility.
We have also recently identified a large membrane-associated protein complex that contains myosin species thought to be required for parasite motility. We are currently analyzing the composition and assembly of this complex, along with the characterization and regulation of the motor activity of the myosin.
Second, we are characterizing the Toxoplasma membrane skeleton, a dense network composed of 10 nm filaments that appears to be crucial for maintenance of the parasites’ shape and integrity. We have characterized the major proteins that make up this network and are analyzing the actual process of filament formation in vitro and network assembly in vivo during parasite cell division.
- Mann, T., Gaskins, E., and Beckers, C. J. (2002). Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii. J. Biol. Chem. 277, 41240-41246.
- Hu, K., Mann, T., Striepen, B., Beckers, C. J. M., Roos, D. S., and Murray, J. M. (2002). Daughter cell assembly in the protozoan parasite Toxoplasma gondii. Mol. Biol. Cell 13, 593-606.
- Moudy, R., Manning, T. J., and Beckers, C. J. (2001). The loss of cytoplasmic potassium upon host cell breakdown triggers egress of Toxoplasma gondii. J. Biol. Chem. 276, 41492-41501.