Therapeutics/Drugs

Luiz Ozaki and Gail E. Christie of Virginia Commonwealth University in the U.S. will genetically engineer bacterial viruses to carry peptides that block the development of the malaria parasites, survive in the mosquito gut, and spread through vector populations. If successful, these bacteriophages could be used as "gene dissemination tools" for effective control of the malaria.

Thomas Baker, Matt Thomas and Andrew Read of Pennsylvania State University in the U.S. will infect malaria mosquitoes with an insect-specific fungus to determine if the infected mosquitoes' sense of smell is suppressed and their ability to find human hosts and transmit malaria is reduced.

When malaria parasites infect different human cells, including liver and red blood cells, it is thought that microRNAs are important developmental cues that facilitate specific events in the parasite life cycle. Jen-Tsan Chi of Duke Medical Center in the U.S. will test whether expressing liver-specific microRNAs within red blood cells will trick the parasite into undergoing liver-stage development, leading to its death.

Marcelo Jacobs-Lorena, of the Johns Hopkins School of Public Health in the U.S. proposes to modify bacteria that naturally inhabit the mosquito midgut to secrete proteins that interfere with the development of the malaria parasite in the mosquito that is necessary for malaria transmission.

Larry Walker of the University of Mississippi in the U.S. will test an innovative approach to mitigate the toxicity of primaquine, a promising and powerful malaria drug. Walker will separate the drug into two components, called isomers, to see if a single form retains the ability to eliminate the malaria parasite in its latent liver stages and the mature gametocytes while reducing toxic side effects.

Erich Cerny of Wissenschaftlicher Fonds Onkologie in Switzerland will test whether inducing antibodies against anti-malarial drugs can significantly prolong the half- life of that drug. Antibodies elicited via immunization may form a reservoir of the active drug for long-lasting treatment for malaria. Such a "small molecule vaccine" has significant implications for efficacy and cost of malaria prevention.

Anders Hakansson of the University of Buffalo in the U.S. has identified a protein from human breast milk (Human Alpha Lactalbumin Made Lethal to Tumor cell, or HAMLET), that kills respiratory tract bacteria. Hakansson will attempt to understand the mechanism by which HAMLET binds to and kills pheumococci without the bacteria developing resistance.

To test the theory that certain metabolic pathways essential to the survival of bacteria are immutable and therefore promising targets of drug therapy, Krishna Kodukula and colleagues at SRI International in the U.S. will identify peptides that bind key metabolites of M. tuberculosis, and test their ability to kill the bacteria.

T. brucei, the parasite that causes sleeping sickness, must continuously swim forward in human blood to evade immune responses. Arthur Günzl of the University of Connecticut Health Center in the U.S. will attempt to develop serum-stable RNA molecules to immobilize the parasite by interrupting the mechanism driving parasite motility.

Alice Telesnitsky of the University of Michigan in the U.S. seeks to define and characterize HIV interactions with host RNA. The team will attempt to determine whether disrupting or mimicking essential interactions with host RNAs may lead to antiviral strategies to which HIV cannot readily develop resistance.