Partner 2

Short name: IPK

Principal Investigator: Dr. Lucio Freitas-Junior, Institut Pasteur Korea

Host Institution. Institut Pasteur Korea (IPK) was formally inaugurated on April 2004 with the strategic focus on enabling technologies and therapeutics development in disease models pertaining to public health in Korea and elsewhere. In the network of international Pasteur institutes, IP-Korea is the first to develop a technology based approach to therapeutics development in close collaboration with foreign partner institutions. Strategically, it combines Insitut Pasteur’s strength in biomedical research with Korean expertise in Information and Nanothechnology. Insitut Pasteur Korea is progressively being consolidated as center of biomedical research and technology development allowing new drugs to be identified faster and more realiably. Insitut Pasteur Korea is divided in 3 major areas: Biology, Technology and Chemistry, and collaborative research among the different areas is not only encouraged but also necessary for accomplishing the institute’s mission.

Dr. Lucio Freitas-Junior is the head of the Systems Biology of Pathogens Group. In IPK, Dr. Freitas-Junior’s group is committed with the discovery of new drugs for deadly parasitic diseases, such as malaria and leishmaniosis. Using a cell-based approach and taking advantage of IPK’s state-of-the-art screening platforms and image mining know-how, Dr. Freitas-Junior and his colleagues are developing visual high-throughput screening assays for finding drugs that target virulence factors transport in malaria parasites. Using a similar approach, an assay is being developed for kinetoplast-directed drug assays for Leishmania parasites, which is in advanced phase of execution (validation). For the present proposal, 4 members from Dr. Freitas-Junior’s lab will be involved in high-throughput screening assay development and execution: Dr. J. L. Siqueira-Neto (postdoc), G. S. Yang (technician), H.R. Oh (technician), and a postdoc to be hired.

Dr. Thierry Christophe is the head of the Screening Technology and Pharmacology Group in IPK. His group works in close collaboration with the biological groups of Institut Pasteur Korea for assay development for drug discovery using large libraries of molecules (usually >100,000) The individual assays are uniquely developed for each disease such that the visual assay mimic disease phenomenon. This is possible thanks to the use of robots that handle the drug libraries, as well as an automated confocal microscope designed for High Content Throughput (Opera reader), which allows the detection virtually any cellular sub-structure and measure fluorescently labeled molecules within the cell. In addition to confocal microscopy readout, the Dr. Christophe's group also develops disease-based assays using more common readout such as fluorescence and luminescence.

Dr. Auguste Genovesio is the founder and head of the Image Mining Research Lab, which is focused on the development of image mining software to extract quantitative information from high throughput cellular imaging. The software exploits image recognition methods to identify new small molecule compounds that effectively treat a wide range of cellular disease models, from malaria and HIV to chronic diseases. Interfacing with biologists and technology developers is an important goal of the group, but the heart of it is computer vision and image data mining.

Selected Publications:

1. Freitas-Junior LH, Hernandez-Rivas R, Ralph SA, Montiel-Condado D, Ruvalcaba-Salazar Rojas-Meza AP, Mancio-Silva L, Leal-Silvestre RJ, Gontijo AM, Shorte S, Scherf A. “Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites.” Cell. 2005 Apr 8;121(1):25-36.

2. Freitas-Junior L, Bottius E, Pirrit LA, Deitsch K, Scheidig C, Guinet F, Nehrbass U, Wellems T, Scherf A. “Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum” Nature, 2000 . 407(6807):1018-22
3. Arheln N*,  Genovesio, A*, et al. « Quantitative 4D tracking of flash-labelled cytoplasmic and nuclear HIV-1 complexes." Nature Methods 2006 3: 817-824. ( * these authors equally contributed to the work)
   Cabal G. G. *, Genovesio A*, et al. "SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope". ( * these authors equally contributed to the work) Nature 441, 770-773.
4. Genovesio, A. Liedl ,T.,et al. "Multiple particle tracking in 3D+t microscopy: Methods and application to the tracking of quantum dots. IEEE Transaction on Image Processing", Volume: 15, Issue: 5,  pp1062- 1070.
5. Signoret N., Christophe T., Oppermann M. and Marsh M. "pH-Independent endocytic cycling of the chemokine receptor CCR5. Traffic, 2004, 5(7) : 529-43.