Comparative Analysis of Cell Death Regulation in Mosquitoes

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DESCRIPTION (provided by applicant): Infectious diseases transmitted through mosquitoes account for millions of death world wide each year. Cell death (apoptosis) is an important component of host/vector immuno-response mechanism and has been implicated in the life cycle of pathogens in mosquitoes. However the understanding of cell death regulation in mosquito was hindered greatly by the fact that major insect cell death regulators, namely the reaper/hid/grim (RHG) like lAP-antagonists identified in Drosophila, were not present in the annotated mosquito (Anopheles gambia) genome. Using a systematic bioinformatics approach, we have identified several candidates of reaper/hid/grim-like lAP-antagonist in both the Anopheles and Aedes mosquito genomes. One of them, michelob_x has been characterized as indeed an lAP-antagonist. This proposed project aims at further characterizing these lAP-antagonists and their role in mediating cell death during mosquito development as well as in response to pathogen infection. Findings generated from this study should significantly improve our understanding of immuno-response and cell death regulation in mosquitoes. It is also quite possible that some of these genes, because of their tissue-ablation activity, can be used for mosquito population control strategies.