Microbiology ETH - Open Positions

Group:	Hardt
Position:	Semesterarbeit / Diplomarbeit
Contact:	Prof. Dr. Wolf Dietrich Hardt Institute of Microbiology Wolfgang-Pauli-Str. 10 HCI G 417 ETH Zürich CH-8093 Zürich Phone: +41(0)44 632 5143 E-mail: hardt@micro.biol.ethz.ch
Description:	Salmonella typhimurium is one of the leading causes of bacterial food poisoning. The project analyzes the pathogenetic mechanisms of Salmonella infections. A protein injection organelle (called typeIII secretion system) is of key importance in the induction of diarrhea because it allows the bacterium to inject protein toxins directly into cells of the host’s intestine. The candidate is going to use cell culture infection experiments to analyze at a molecular level how the injected Salmonella toxins manipulate host cell signaling pathways. So we have found that one of the protein toxins (SopE) injected into host cells acts as a specific G-nucleotide exchange factor (Hardt et al., 1998). SopE specifically activates Cdc42- and Rac1-signalling inside the host cell (all references). However, besides SopE, S. Typhimurium injects at least 12 additional protein toxins into host cells which contribute to the manipulation of host cellular signaling (i.e. actin polymerization, intracellular Ca²⁺- and phosphatidylinositol-levels, chloride secretion) pathways in unknown ways. The project is going to analyze the function of two Salmonella toxins, which have not been characterized so far. It will involve recombinant DNA techniques, tissue culture, immunofluorescence microscopy (including live cell imaging), transient transfection experiments, cell biology and protein purification. Literature: Buchwald, G., A. Friebel, J. E. Galan, W. D. Hardt, A. Wittinghofer, and K. Scheffzek. 2002. Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE. EMBO J 21:3286-95. [Abstract] Friebel, A., H. Ilchmann, M. Aelpfelbacher, K. Ehrbar, W. Machleidt, and W. D. Hardt. 2001. SopE and SopE2 from Salmonella typhimurium activate different sets of RhoGTPases of the host cell. Journal of Biological Chemistry 276:34035-40. [Abstract] Hardt, W. D., L. M. Chen, K. E. Schuebel, X. R. Bustelo, and J. E. Galan. 1998. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93:815-26. [Abstract] Rudolph, M. G., C. Weise, S. Mirold, B. Hillenbrand, B. Bader, A. Wittinghofer, and W. D. Hardt. 1999. Biochemical analysis of SopE from Salmonella typhimurium, a highly efficient guanosine nucleotide exchange factor for RhoGTPases. J Biol Chem 274:30501-9. [Abstract] Schlumberger, M. C., A. Friebel, G. Buchwald, K. Scheffzek, A. Wittinghofer, and W. D. Hardt. 2003. Amino acids of the bacterial toxin SopE involved in G-nucleotide exchange on Cdc42. J Biol Chem. 278:27149-59. [Abstract]
Time frame:	as agreed

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