Malaria

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.

Andrew Fung, Jack Judy and Theodore Moore at the University of California, Los Angeles in the U.S., along with Michel Bergeron of l'Université Laval in Canada, will work to identify molecular markers of malaria present in saliva in order to develop a chewing gum diagnostic tool called "MALiVA." During chewing, particles in the gum will react with these malaria proteins, which can be detected and characterized when this device is scanned with a magnet.

David Wright of Vanderbilt University in the U.S. will develop a new low-cost diagnostic tool in which a droplet of malaria-infected blood deposited on a glass slide will, based on fluid dynamics, leave a ring-like pattern as the blood evaporates. The slide will be prepared with a solution that will interact with a particular protein of the malaria parasite to visualize this "coffee ring stain," allowing for easy interpretation and ready diagnosis.

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.

Antimicrobial peptides (AMPs) are essential components of the innate immune system that provides resistance to a variety of pathogenic organisms by selectively lysing, or bursting, cellular membranes of invading pathogens. Doron Greenbaum of the University of Pennsylvania in the U.S. will test whether small molecules that mimic the natural AMPs can selectively kill the parasite that causes malaria. Such an approach could reduce costs of production as well as limit the emergence of drug resistance.

Bongkoch Tarnchompoo of the National Center for Genetic Engineering and Biotechnology in Thailand will attempt to develop and test a novel drug that binds to the two pathways used by the DHFR enzyme in P. falciparum to mutate. By tethering these active sites, the dual-binding drug will suppress the development of resistance to anti-malarial drugs.

Carmenza Spadafora of Panama's Institute of Advanced Scientific Investigations and High Technology Services and José A. Stoute of Pennsylvania State University College of Medicine in the U.S. investigated whether malaria can be treated by microwave irradiation, an idea based on the unique electromagnetic properties of hemozoin, a metabolite formed by Plasmodium parasites in infected red blood cells. This project's Phase I research demonstrated that malaria parasites inside red blood cells are sensitive to low doses of microwaves that do not harm uninfected red blood cells.

To fight emergence of drug and vaccine resistance in rapidly evolving parasites, Pradipsinh K. Rathod of the University of Washington in the U.S. will identify the parts of the malaria genome which contribute to rapid increases in mutations, and will screen for small molecules that inhibit these mechanisms. This project's Phase I research demonstrated that hypermutagenesis does play a strong role in the development of drug resistance.

Alison McCormick of Touro University, California in the U.S. will test the ability of a low-cost plant-based synthetic biology method to produce a combined viral protein epitope with an antigen RNA expression system for use in an RNA malaria vaccine. Using plants for this viral transfection system could make RNA vaccine production scalable and cost effective.

Andreas Matouschek and Keith Tyo of Northwestern University in the U.S. will develop synthetic compounds that target essential proteins in the Plasmodium parasite for destruction by its own protein degradation mechanisms. This strategy could aid new small molecule drug development efforts to combat malaria.