Comparative Analysis of Cell Death Regulation in Mosquitoes

描述(申请人提供)：通过蚊子传播的传染病每年导致全球数百万人死亡。细胞死亡(细胞凋亡)是宿主/媒介免疫应答机制的重要组成部分，参与了蚊虫病原体的生活史。然而，主要的昆虫细胞死亡调节因子，即果蝇中发现的类似LAP拮抗剂的REAPER/HID/GRIM(RHG)，并不存在于注释蚊子(Anopheles冈比亚)的基因组中，这一事实极大地阻碍了人们对蚊子细胞死亡调控的理解。利用系统的生物信息学方法，我们已经在按蚊和伊蚊基因组中确定了几个收割者/HID/GRIM样LAP拮抗剂的候选基因。他们中的一位，Michelob_x被描述为一个真正的LAP对手。这项拟议的项目旨在进一步表征这些LAP拮抗剂及其在蚊子发育过程中调节细胞死亡以及对病原体感染的反应中的作用。这项研究的结果将大大提高我们对蚊子的免疫反应和细胞死亡调节的理解。其中一些基因由于其组织消融活性，也很有可能被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.