LEISHDRUG Consortium

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Partner 8

Short name: CSIC

Principal Investigator: Dr. Luis Rivas, Centro de Investigaciones Biológicas (CSIC), Madrid.

Host Institution. The Consejo Superior de Investigaciones Científicas (CSIC) is the largest public multidisciplinary research organisation in Spain. It has a staff of more than 10000 employees, among these 3202 scientists and about 3802 pre and postdoctoral researchers. The CSIC has 116 Institutes or centres distributed throughout Spain.There is also a delegation in Brussels. It has considerable experience in both participating and managing R&D projects and training grants. Under the 6th Framework Programme, the CSIC has signed 418 contracts (37 coordinated by the CSIC). The CSIC is the 5th organisation in Europe in project execution and funding.

Dr Luis Rivas obtained his PhD in Chemistry (Biochemistry) at the University of Madrid, 1984, followed by postdoctoral periods at the Weizmann Institute (Prof C. Gitler) and Yale University (Prof D. McMahon-Pratt), working on the biochemistry of Entamoeba and biochemistry and immunology of Leishmania, respectively. In 1986 he obtained a permanent staff position in the CSIC and currently he heads the Antimicrobial Peptide Group of the Center for Biological Research (CIB) in Madrid. His current activity is focused both on the screening, design and optimization of antimicrobial peptides (AMPs) as new antileishmanial and macrophage activating agents, in close collaboration with Prof. David Andreu (UPF, Barcelona), as well as in the target elucidation for new and standard leishmanicidal drugs, including AMPs acting through intracellular targets, specially those acting on the bioenergetic metabolism of the parasite The CIB has state of the art facilities for electron and confocal microscopy, protein chemistry, spectroscopy and proteomics, among others. Other members of the team are: Maria E Carrillo (Ph.D. Biology, postdoc) and María Fernández-Reyes(Ph.D. student), working on the role of cell penetrating peptides on Leishmania and in the assay of new antimicrobial peptides, respectively. One postdoc will be hired to carry out the assays for kinase inhibition.

Selected Publications:

1. Saugar, J. M., Delgado, J., Hornillos, V., Luque-Ortega, J. R., Amat-Guerri, F., Acuna, A. U., and Rivas, L. (2007) Synthesis and biological evaluation of fluorescent leishmanicidal analogs of hexadecylphosphocholine (miltefosine) as probes of antiparasite mechanisms. J Med Chem accepted (JM 070595+).

2. Luque-Ortega, J. R., and Rivas, L. (2007) Miltefosine (hexadecylphosphocholine) inhibits cytochrome c oxidase in Leishmania donovani promastigotes. Antimicrob Agents Chemother. 51, 1327-1332

3. Mangoni, M. L., Papo, N., Saugar, J. M., Barra, D., Shai, Y., Simmaco, M., and Rivas, L. (2006) Effect of natural L- to D-amino acid conversion on the organization, membrane binding, and biological function of the antimicrobial peptides bombinins H. Biochemistry 45, 4266-4276

4. Arias, C., Guizy, M., Luque-Ortega, J. R., Guerrero, E., de la Torre, B. G., Andreu, D., Rivas, L., and Valenzuela, C. (2006) The induction of NOS2 expression by the hybrid cecropin A-melittin antibiotic peptide CA(1-8)M(1-18) in the monocytic line RAW 264.7 is triggered by a temporary and reversible plasma membrane permeation. Biochim. Biophys. Acta 1763, 110-119

5. Mangoni, M. L., Saugar, J. M., Dellisanti, M., Barra, D., Simmaco, M., and Rivas, L. (2005) Temporins, small antimicrobial peptides with leishmanicidal activity. J. Biol. Chem. 280, 984-990.