Anion Regulation in Larvae of Disease Vector Mosquitoes

描述（由申请人提供）：长期目标是表征蚊子幼虫肠道上皮细胞的关键功能，因为这些细胞功能影响和调节肠腔碱化的阴离子基础。详细了解肠道上皮细胞如何产生驱动消化过程的显着和生物学上独特的pH值极端（即> 10.5），将为开发环境安全和特定的幼虫提供新的途径。在肠道碱化过程中，碳酸酐酶和跨膜阴离子转运蛋白这两个特定的基因家族在阴离子的产生和运输中起着核心作用，因此成为研究的目标。该项目将产生这两个基因家族成员的分子和生理特征。它们在组织中的分布和在蚊子幼虫肠道碱化中的具体作用将被确定。将定义整个肠道的特定细胞表型，并评估每个细胞在碱化过程中的作用。AIM 1将检测多种碳酸酐酶的表达。AIM 2将定义和表征阴离子转运基因家族的成员。AIM 3将确定肠道中碳酸酐酶和阴离子转运蛋白的细胞分布以及幼虫发育的功能。AIM 4将对蚊子幼虫肠道特定功能域的基因表达进行全球分析，确定确定肠道功能域的关键功能。AIM 5将把特定基因产物的定位与单个细胞活性的生理测量结合起来，对肠道上皮中的阴离子动力学进行细胞特异性和空间分析。由于蚊子是全世界人类健康的头号威胁，并被认为是生物恐怖主义的潜在媒介，因此根据蚊子生物学的独特方面（即肠道碱化）制定新的控制战略具有重要的潜力。

DESCRIPTION (provided by applicant): The long term objective is to characterize key functionalities of the epithelial cells of the larval mosquito gut as these cellular functions influence and regulate the anionic basis of alkalinization of the gut lumen. A detailed understanding of how gut epithelial cells produce the remarkable and biologically unique pH extremes (i.e. > 10.5) that drive the digestive process will provide new avenues for the development of environmentally safe and specific larvacides. Two specific gene families have been targeted as they have central roles in anion production and transport in the gut alkalinization process: carbonic anhydrases and transmembrane anion transporters. This project will produce molecular and physiological characterizations of members of these two gene families. Their distributions in the tissue and specific roles in larval mosquito gut alkalinization will be defined. Specific cellular phenotypes throughout the gut will be defined and the role of each in the alkalinization process assessed. AIM 1 will examine the expression of multiple carbonic anhydrases. AIM 2 will define and characterize members of the anion transporter gene family. AIM 3 will define the cellular distributions of carbonic anhydrases and anion transporters in the gut and as functions of larval development. AIM 4 will produce a global analysis of gene expression in the specific functional domains of the larval mosquito gut identifying key functionalities which define the gut domains. AIM 5 will bring the localization of specific gene products together with physiological measurements of the activity of individual cells to produce a cell-specific and spatial analysis of anion dynamics in the gut epithelium. As mosquitoes are the number one threat to human health world wide and recognized as potential agents for bioterrorism, the development of new strategies for control based on unique aspects of their biology (i.e. gut alkalinization) has important potential.