Principal Investigators: Dr. Gerald Spaeth , Dr. Geneviève Milon, Dr. Spencer Shorte, Dr. Sylvie Pochet, Institut Pasteur

Host Institution. The Pasteur Institute is a private non-profit foundation whose main fields of activities are research, education and public health. The Institute is a world leader for the research in Infectious Diseases and coordinates an international network of 31 Pasteur Institutes that are mainly localized in endemic areas pertinent to trypanosomatid infections. The campus in Paris has 10 research departments and 16 core facilities including cytometry, dynamic imaging, high-throughput production of protein, proteomics, genomics, animal and BSL3 facilities. Collaborations between teams on campus are encouraged by financial support (Programme Transversal de Recherche, PTR) and support for the exploitation of the biotechnological potential of new technologies and know-how is assured by the new business incubator (Bio Top) present on campus. Exchanges with the industry are guaranteed by privileged industry-academia collaborations.

Four separate laboratories of IP are implicated in the LEISHDRUG consortium.

Dr. Gerald Spaeth is the head of the Laboratory of Parasite Virulence in the Department of Parasitiology and Mycology at the Pasteur Institute in Paris. His laboratory uses genetic and proteomic methods to identify Leishmania signaling pathways implicated in pathogenicity and to validate components of these pathways as potential target molecules for the development of novel anti-leishmanial strategies. The laboratory is equipped with a state-of-the art proteomics platform, and four lab members with complementary expertises are implicated in the proposal: Dr. M. Morales (postdoc) and R. Watanabe (technician) carry out phosphoproteomic studies, Dr. D. Schmidt-Arras investigates the interaction of Leishmania kinases with their phospho-protein substrates, and Wai-Lok Yau (Ph.D. student) generates signaling deficient Leishmania.

Dr. Geneviève Milon is currently the head of the Immunophysiology and Parasitology Unit within the Department of Parasitology and Mycology at the Pasteur Institute in Paris.The research of Geneviève Milon (DVM) and her Colleagues (T.Lang/H.Lecoeur/E.Prina) is curiosity/hypothesis-driven their main objectives being to decipher the features of parasitism at the tissue, cellular subcellular and molecular level. In their laboratory many robust and relevant systems have been set up. Of peculiar importance within the present call is the generation of transgenic Leishmania expressing reporter molecules such as luciferase and/or fluorescent proteins – GFP/ Dsred2-.The latter are relevant living probes for in vivo real time imaging and/or in vitro visual screening of any components specifically targeting cell-cycling amastigotes within the Parasitophorous Vacuoles of the mammal phagocytic leucocytes that are subverted as bona fide host cells.

Dr. Spencer Shorte was appointed group leader at the Institut Pasteur (Paris) where he set-up the Platform for Dynamic Imaging Studies (www.pfid.org) that applies and develops optical imaging techniques for studies on infectious disease processes. In 2006, he was appointed director to the Imagopole (www.imagopole.org) that harbours expertise for microscopic, ultra structural and cytometry imaging technologies applied to infection. He is author to more than thirty research articles, learned reviews, and numerous patents and editor to the recently published book "Imaging Cellular & Molecular Biological Functions" (Springer, 2007). His work on Micro-rotation imaging received the 2005 French engineer of the year prize, and is funded by the European Union FP6 program.

Dr. Sylvie Pochet is currently the head of the Organic Chemistry Unit within the Department of Structural Biology and Chemistry at the Institut Pasteur (Paris). The main purpose of our research program is the design and synthesis of new chemical entities targeting nucleoside metabolism enzymes and the identification and characterization of unexplored targets related to this metabolism .. In 2006 a versatile automated screening plateform was set-up under the supervision of H. Munier-Lehmann and available for collaborative projects. Compounds from various origins are evaluated for their potential inhibitory activity on purified enzymes or cellular assays. Molecules developed in-house or from collaborative studies are regularly added to the « Organic Chemistry Unit » chemical library.

Morales M.A., Watanabe R., Laurent C., Lenormand P., Rousselle J.C., Namane A. and G.F. Späth, “Phosphoproteomic analysis of L. donovani pro- and amastigote stages”, Proteomics 2007, in press.
Morales M.A., Renaud O., Faigle W., Shorte S.L. and G. F. Späth, “ Over-expression of Leishmania major MAP kinases reveals stage-specific induction of phosphotransferase activity”, Int. J. of Parasitology, 2007, 11:1187-99.
Lang T, Goyard S, Lebastard M, Milon G, “Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice”, Cell Microbiol. 2005 Mar;7(3):383-92.
Renaud, O., Vina, J. Yong, Y. Machu, C., Trouvé, A., Van der Voort, H., Chalmond, B. and Shorte, S., “High-resolution imaging of living cells in flow suspension using axial-tomography : 3D imaging flow cytometry”, Biotechnology J. 2007 (in press).
Renaud, O., Heintzmann, R., Saez-Cirion, A., Schnelle, T., Mueller, T. and Shorte, S. (2007). A system and methodology for high-content visual screening of individual intact living cells in suspension, vol. 6441 (ed. L. F. Daniel C. L. Robert and V. N. Dan), pp. 64410Q: SPIE.