Enabling Drug Discovery for Malaria

Malaria is responsible for 300 million cases a year, resulting in 1 million deaths. From a military perspective, maintaining bases in regions where the disease is endemic puts troops at risk for infection. Whether for civilian or military populations,the fact remains that insecticide tolerant mosquitoes, drug resistant parasites and lack of effective vaccines necessitate new approaches to combating this scourge. Emerging information about the genetics of these organisms, primarily through advances inwhole-genome and expression analysis, provides a knowledge base to investigate new opportunities for disease prevention. Genetic approaches are complemented by technological advances in high-throughput screening and combinatorial chemistry that, together,enable a means to synthesize and rapidly screen prospective drug leads. In this Phase I proposal, Agave BioSystems proposes to develop a validated protocol for the isolation of shikimate pathway genes from P. falciparum, the causative agent of malaria.The success of this approach will allow isolation of other metabolic genes of interest, extending the number of enzymes that can be targeted for drug discovery efforts to effectively combat this global disease. The worldwide market for drugs to combatmalaria is significant. This program will establish the core technology to validate genes isolated from this particular group of organisms and express and isolate them in recombinant form to enable drug discovery. This process can then be used to developdrugs for other significant pathogens.