Comparative Analysis of Cell Death Regulation in Mosquitoes

描述（由申请人提供）：通过蚊子传播的传染病每年在全世界造成数百万人死亡。细胞死亡（凋亡）是宿主/媒介免疫应答机制的重要组成部分，并与蚊子中病原体的生命周期有关。然而，对蚊子中细胞死亡调节的理解受到以下事实的极大阻碍：在果蝇中鉴定的主要昆虫细胞死亡调节剂，即reaper/hid/grim（RHG）样IAP拮抗剂，不存在于注释的蚊子（冈比亚按蚊）基因组中。使用系统的生物信息学方法，我们已经确定了几个候选人的收割机/隐藏/grim样IAP拮抗剂在按蚊和伊蚊基因组。其中michelob_x是一种IAP拮抗剂。该项目旨在进一步表征这些IAP拮抗剂及其在蚊子发育期间介导细胞死亡以及响应病原体感染中的作用。从这项研究中产生的发现应该显着提高我们对蚊子免疫应答和细胞死亡调节的理解。这些基因中的一些也很有可能因为它们的组织消融活性而用于蚊子种群控制策略。

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.