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	2008 Fellow			Hector A. Saka, Ph.D. Laboratory of Raphael Valdivia, Ph.D. Dept. of Molecular Genetics & Microbiology Duke University 272 Jones Bldg., Box 3580 Durham, NC 27710 Phone: (919) 668-3831 Fax: (919) 681-9193 Email: has1237@gmail.com

Country: Argentina

Field: Microbial Pathogenisis/ Cell Biology

Research Interest: Identification of the molecular mechanism underlying the subversion and sequestration of host cytoplasmic lipid droplets by the obligate pathogen Chlamydia trachomatis. The obligate intracellular bacterial pathogen Chlamydia trachomatis is responsible for a range of ocular and genital infections of significant clinical importance. The pathogen multiplies in epithelial cells within a membranebound vacuole named the inclusion. Though it is a crucial step in their pathogenesis, the mechanisms used by Chlamydiae to transport nutrients into the inclusion are poorly characterized. Studies with pharmacological inhibitors indicate that the acquisition of host cellderived lipids into the inclusion is essential for bacterial replication. In eukaryotic cells, lipid droplets (LD), organelles consisting in a core of neutral lipids, constitute the main store of lipids. In Chlamydia infected cells, LDs accumulate at the periphery of the inclusion in a process mediated by C. trachomatis proteins, strongly suggesting that Chlamydia targets LDs to obtain a source of lipids. Recent findings made by Dr. Valdivia's group, indicate that C. trachomatis translocates intact cytoplasmic LDs into the inclusion lumen. This represents the first example of mammalian LD functions being coopted by a bacterial pathogen. In this project, I propose to perform a molecular characterization of this completely novel pathogenic mechanism. To achieve this, I will use siRNA technology and classical cell biology techniques to determine the role of cytoskeletal motors and other host cell proteins involved in vesicular transport (eg. Rab and Rab effectors) in regulating LD translocation into the inclusion lumen. Furthermore, I will apply proteomic techniques to identify bacterial and host factors involved in this phenomenon. The completion of this project will provide new insights into the molecular basis of how C. trachomatis manipulates the host cell to subvert LDs and the cell biology of these understudied organelles.