Therapeutics/Drugs

Paul Gilson of Macfarlane Burnet Institute for Medical Research and Public Health in Australia will study the function of a newly discovered malaria parasite mechanism that exports proteins into host red blood cells in an effort to develop compounds that block this transfer and inhibit parasite growth.

Simon Foote of the Menzies Research Institute at the University of Tasmania in Australia will use "forward genetic screening" approaches identify mutations that confer resistance after exposure to malaria parasites. The team will use this powerful information to develop drug therapies that target the human host and mimic these protective genetic effects.

Philip J. Shaw of Thailand's National Center for Genetic Engineering and Biotechnology will seek to identify potential drug targets and vaccine antigens in the malaria parasite using a novel technology to reduce specific gene expression. By fusing a natural genetic "riboswitch" onto gene targets, the team will attempt to attenuate gene expression and thereby determine gene function.

Lourival Possani of the Institute of Biotechnology at the National University of Mexico will investigate the antimalarial effects of scorpine, a newly identified peptide found in the venom of scorpions. The team will test scorpine's efficacy in blocking K+ channels used by malaria parasites to replicate in mosquitoes. Creating a new generation of malaria-resistant mosquitoes can aid in the eradication of the disease in humans.

Richard Sayre of Donald Danforth Plant Science Center in the U.S. will develop and test a transgenic algae that delivers interference RNA (RNAi) elements to mosquito larvae when they feed on it. These RNAi will silence essential genes used by the larvae to develop, thus killing mosquitoes before they can transmit malaria.

Victor Nussenzweig of the New York University School of Medicine in the U.S. seeks to develop a small molecule drugs to inhibit key kinase enzymes in the malaria parasite that are thought to control latency in parasite infections. Such fundamental knowledge may enable new tools to clear the latent forms of P. vivax parasites or block transmission of the disease by targeting sporozoites.

Matthias Marti of the Harvard School of Public Health in the U.S. will utilize a newly developed transgenic malaria parasite that expresses GFP indicating when the parasites are ready to be transmitted to mosquitoes. He will use this technology to screen for compounds that can prevent the development of these gametocytes.

Moriya Tsuji of the Aaron Diamond AIDS Research Center in the U.S. will test whether the human malaria parasite can infect mice engineered with humanized livers and red blood cells by producing human erythropoietin. The goal of this project is part of a larger effort to create a mouse model capable of supporting the full malaria life cycle for use in preclinical testing of new anti-malarial therapies and vaccines.

Michael Leibowitz of the UMDNJ-Robert Wood Johnson Medical School in the U.S. will investigate whether malaria parasites bind to, invade and replicate in the endothelial cells that line the blood vessels to test the theory that endothelial cells play an important role in the development of malaria infection and may serve as undiscovered reservoirs for parasite latency.

Joseph Vinetz of the University of California, San Diego in the U.S. will attempt to create a new mouse model that mimics both human liver and blood cell function. These new mouse models should allow human malaria parasites to complete their full life cycle in the models and provide a new tool for testing anti-malarial strategies, including drugs and vaccines.