RESEARCH SUMMARY

Figure 1.

Toxoplasma gondii is a ubiquitous pathogen infecting one-third of the US population. It is frequently responsible for congenital neurological defects, and becomes a lethal disease in immunocompromised adults. Toxoplasma causes disease only when it can replicate: blocking parasite replication completely prevents disease. We study the cell biology of parasite replication. The question we ask is simple: "How do you build a parasite?"

One aim is to use the answers to this question in the search for more effective therapy. A second aim is to exploit the unique advantages of Toxoplasma as a model system for elucidating fundamental cell biological processes common to all organisms.

Toxoplasma , like its close relative Plasmodium, the agent of malaria, replicates by a distinctive process in which multiple daughters assemble simultaneously within the mother cell, a process in which assembly of the cytoskeleton is critical. Our major focus is the regulation of parasite replication, and the assembly of the cytoskeleton.

Figure 2.

With fluorescent reporter proteins and advanced imaging techniques we analyze the development of various subcellular organelles over time, using video microscopy, image deconvolution, confocal microscopy, fluorescence photobleaching, and laser ablation. Our goal is to determine the chronological order of critical events in T. gondii replication, the cause and effect relationships among these processes, and the molecular mechanisms involved.

Toxoplasma utilizes the ubiquitous cytoskeletal protein tubulin to form a novel molecular machine that is probably involved in parasite invasion. The Toxoplasma-specific features of this organelle make it a target for specific therapy. The highly conserved features make it an excellent model for unraveling the function of critical tubulin-based molecular machines found in all cells. We study the composition of these cytoskeletal assemblies using mass spectroscopy and proteomics, and their structure using high-resolution cryo-electron microscopy.

Click here for a list of publications (searches the National Library of Medicine's PubMed database.)