Functional genomic analysis of Anopheles gambiae innate immunity and interaction with the malaria parasite. (360G-Wellcome-077229_Z_05_A)

Anopheline mosquitoes are obligatory vectors of human and other mammalian malaria parasites of the genus Plasmodoum. This research programme will capitalize on the newly available genome sequence of Anopheles gambiae, the major human malaria vector in Africa, and on postgenomic tools (many developed in our laboratory) to understand the mosquito innate immune system and its interactions with the rodent and human parasites (P. berghei and P. falciparum). Our recent work has established that innate immunity is a major determinant of the mosquito's vectorial capacity: Anopheles immune reactions account for substantial parasite losses during invasion of the mosquito midgut, but often allow immune escape and parasite transmission. We aim to elucidate key immune reactions, including parasite lysis and melanisation, at the molecular and cellular level. We wish to reveal the molecular module underlying each major immune reaction, to dissect its effector or regulatory functional networks and their molecular components (genes/proteins), and ultimately to understand the operation of each module as a whole. This work will contribute significantly to the emerging comparative understanding of innate immune mechanisms and may open future possibilities for controlling malaria transmission in the vector.