Protein Synthesis/Developmental Transitions in Plasmodiu

Niaid Extramural Activities

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Abstract

Vector-borne diseases, like malaria are major public health problem throughout the world. The extent of disease is largely a function of fluctuation in the vector populations. Our central objective is to interrupt the transmission cycle of malaria by altering the natural balance of refractory/transmission competent mosquitoes in local populations. We have taken two different approaches. Previous work in the laboratory has shown that the ribosomes of malaria parasites use structurally unique sites for the catalysis of protein synthesis. We have shown that these can be selectively targeted during parasite development in the mosquito. The two most promising sites of attack are the GTPase site and the pseudoknot of these ribosomes which are both important drug targets for antibiotics. A transmission blocking drug would serve reduce the number of carriers and slow dispersal of the disease. Another approach which we are actively pursuing is to interrupt the transmission cycle of malaria by altering the natural balance of refractory/transmission competent mosquitoes in local populations. We have 4 specific aims: 1) the establishment of a base line at test sites using both new and established technology. 2) The collection and expansion of ?outbreed? lines of refractory mosquitoes. 3) Isolation of genes associated with the refractory phenotype. 4) Fitness testing of the refractory mosquitoes; first in contained ?biosphere conditions and then after release of mosquito larva into the environment. We feel that the outcome will be an inexpensive and environmentally sound way to control malaria transmission that will be adaptable to other vector borne diseases. To date we have developed the technology to follow transmission levels in field situation which should be widely applicable. We have also shown that infected mosquitoes can be separated from malaria refractory mosquitoes using temperature gradients. This is based upon a phenomenon called behavioral fever. Mosquitoes that are infected seek out warmer temperatures on a temperature gradient and hence can be separated from uninfected and refractory mosquitoes. We have developed collaborations with Kenyan scientists to adapt these technologies to field research.