: Toxoplasma gondiiis a cosmopolitan intracellular protozoan whose success as a pathogen is attributable to the creation of a nonfusogenic parasitophorous vacuole (PV). Endocytosed within the PV, parasites replicate in a niche sequestered from host cell endocytic and exocytic traffic. This unique compartment is established during invasion, which effects the intimate apposition of host cell and parasite plasma membranes. The intercellular interface, the """"""""moving junction,"""""""" is likely the primary regulator of PV membrane (PVM) composition and PVM nonfusogenicity, hence, parasite survival. Remarkably, since its discovery decades ago, this membranous contact region between host and parasite has remained largely uncharacterized with regard to precise function, macromolecular organization, and biochemical content. This proposal will test the hypothesis that the moving junction is a biochemically-defined entity that governs the initial attributes of the protective vacuolar membrane.The first specific aim will demonstrate that the moving junction selectively directs the entry of cholesterol and charged phospholipids into the PVM and sorts host cell transmembrane proteins by virtue of membrane microdomain association. The second specific aim will test whether the moving junction is itself comprised of lipid rafts. Finally, the third specific aim will utilize an elegantly designed strategy to identify host cell and parasite moving junction proteins. Progress in these endeavors promises to augment our appreciation of the complexity of this specialized heterotypic junction, and to leave us poised to utilize this knowledge to combat a particularly pernicious phylum of intracellular human pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI050349-01
Application #
6406350
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Rogers, Martin J
Project Start
2001-07-01
Project End
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
Washington University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Charron, Audra J; Sibley, L David (2004) Molecular partitioning during host cell penetration by Toxoplasma gondii. Traffic 5:855-67
Charron, Audra J; Sibley, L David (2002) Host cells: mobilizable lipid resources for the intracellular parasite Toxoplasma gondii. J Cell Sci 115:3049-59