Recent advances in Anopheles gambiae transgenic and high throughput genomic technologies have rendered it a powerful model organism for the study of host - parasite interactions and innate immunity. In addition, Anopheline mosquitoes transmit one of the most serious diseases of mankind, malaria. The lack of effective vaccines, the development of parasite resistance to drugs and mosquito resistance to insecticides contribute to the expansion of the disease and have thereby created an acute need for the development of additional novel control strategies. Control strategies based on the blocking of Plasmodium's lifecycle in the vector mosquito will require the understanding of the molecular mechanisms implicated in mosquito - parasite interactions. The mosquito's innate immune system is capable of killing large numbers of malaria parasites. Ingestion of malaria infected blood results in the activation of innate immune responses that contribute significantly to the killing of Plasmodia in the midgut. The specific elicitors of these immune responses, the immune pathways they regulate and their plasmodiocidal activity on the different stages of the parasite are as yet unknown. This application will utilize a full genome microarray for a comprehensive dissection of the systemic and midgut specific transcript responses to the different components (elicitors) that are associated with malaria infected blood and then assess the impact of these responses on Plasmodium development. These analyses will elucidate important aspects of the mosquito's infection responsive physiology and provide information on the regulation of antiplasmodial immune response. It will provide baseline assessment on the utilization of the mosquito's innate immune system for the development of malaria control strategies.
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