Malaria

Jacquin Niles of the Massachusetts Institute of Technology in the U.S. is developing a method to switch individual genes on and off in the malaria-causing parasite Plasmodium falciparum for evaluating candidate and existing antimalarial drugs. In Phase I, they built and tested a scalable TetR-aptamer system for rapidly and easily manipulating gene expression in the parasite genome, and showed that it could be used to validate the target of a 4-aminoquinoline antimalarial drug.

Manuel Llinás of Pennsylvania State University in the U.S. will characterize the 400 candidate anti-malarial compounds in the so-called "Malaria Box" by mass spectrometry to help select those likely to be the most effective drugs for clinical development. The Malaria Box is a collection of compounds that display some anti- parasitic activity, but how they work and whether they would make valuable new anti-malarial drugs are unknown. They will analyze red blood cells infected with the malarial parasite P.

Koen Dechering of TropIQ Health Sciences in the Netherlands is developing a high-throughput functional assay to identify new compounds that specifically block transmission of the malaria parasites to their vector hosts, which is a difficult stage to target, and to test candidate drugs. The assay incorporates luciferase- expressing parasites, which emit light as they develop in the mosquito midgut, along with barcoded chemical libraries.

Miguel Prudencio of Instituto de Medicina Molecular in Portugal  will test the theory that modified live rodent malaria parasites (P. berghei) can be used in a vaccine to elicit a strong immune response in humans without being able to infect human red blood cells and cause illness.

Consuelo De Moraes, Mark Mescher and Andrew Read of Pennsylvania State University in the U.S. will test the theory that malaria infection induces characteristic odor cues, even in asymptomatic individuals. By identifying these chemical cues with gas chromatography and mass spectrometry, De Moraes will determine if there are biomarkers for diagnosis of infection.

Rebecca Richards-Kortum of Rice University in the U.S. will measure light scattered by malaria-infected red blood cells using a small microscope that can be placed on the skin as a way to detect infection in patients without the need to draw blood. This rapid and painless diagnostic would not require consumable reagents or a trained operator, and would not generate biohazardous waste.

William Gordon and collaborators at Tetragenetics, Inc. in the U.S. propose using T. thermophilia, a fresh-water protozoa commonly used in basic research, to produce malaria antigens in a crystalline protein gel. The close evolutionary relationship between T. thermophilia and protozoan malaria parasites may allow the antigens to retain their natural conformation. In this way, multiple vaccine components can be readily harvested as a single, low-cost, high-potency vaccine formulation. This project's Phase I research demonstrated that T.

Ronald Quinn of Griffith University's Eskitis Institute in Australia and colleagues are seeking to discover chemical fragments drawn from a variety of natural sources that bind to proteins expressed by the malaria parasite in its latent stage and the tuberculosis microorganism. In their Phase I and Phase II research, the team is working on identifying compounds that target proteins involved in key metabolic and energy pathways of latency as the basis for new drug therapies.

Manoj Duraisingh of the Harvard School of Public Health in the U.S. will use RNAi screening to identify critical determinants in human red blood cells (erythrocytes) that are required for invasion and growth of the malaria parasite, Plasmodium falciparum. In this project’s Phase I research, Duraisingh’s group developed a RNAi-based approach for genetic analysis of the erythrocyte in vitro, and demonstrated that the major surface protein Glycophorin A is required for efficient invasion by some strains of P. falciparum.

Louis Schofield of The Walter and Eliza Hall Institute in Australia will develop a synthetic saccharide-conjugated vaccine that would provide immunity against GPI, a toxin produced by the malaria parasite that is a major determinant in the severity and fatality of the disease. This project’s Phase I research demonstrated preclinical safety and efficacy of a synthetic anti-toxin vaccine for malaria, showing that the oligosaccharide target was conserved across all malaria species and life stages.