Pilot Studies in Biochemistry of Anopheles gambiae

描述(申请人提供)：由蚊子传播的人类疾病对热带国家的人口有严重的负面影响，也影响温带地区的人口(例如，最近在北美出现的西尼罗河病毒)。冈比亚按蚊是撒哈拉以南非洲疟疾寄生虫的主要传播媒介。更好地了解冈比亚按蚊的生物学可能有助于改进阻断疟疾传播和控制其他人类疾病蚊子媒介的战略。冈比亚按蚊基因组DNA序列的最近公布是一项重大成就，应该会使这种蚊子基因产物功能的分子研究迅速取得进展。这项由研究人员发起的小额研究补助金的提议是启动对AN中两组蛋白质的生物化学的初步研究。冈比亚亚科：蛇类和漆酶。Serpins是一种丝氨酸蛋白酶抑制剂，具有调节昆虫免疫反应的潜力。然而，它们在蚊子中的功能尚未确定。漆酶是一种铜氧化酶，可以氧化二酚和其他类型的底物。漆酶可能在昆虫角质层硬化或免疫中起作用，但以前很少有人对它们进行生化研究。本项目的目的是从An.获得5个漆酶样蛋白基因和一组精选的14个丝氨酸蛋白基因的全长c DNA克隆。并使用这些DNA作为探针来研究基因的表达和生产用于启动生化研究的重组蛋白。这些目标旨在产生初步成果，以支持未来关于一个国家的更广泛的提案。冈比亚蛇类和漆酶。这个项目将是为PI(蚊子生物化学)开发一个新的研究领域的一个开始，这个领域将建立在他在其他昆虫类生物化学方面的经验基础上。

DESCRIPTION (provided by the applicant): Human diseases transmitted by mosquitoes have serious negative impacts on populations in tropical countries and also affect populations in temperate regions (for example, the recent emergence of West Nile virus in North America). Anopheles gambiae is a major vector of malaria parasites in sub-Saharan Africa. Better understanding of the biology of A. gambiae may lead to improved strategies for disrupting malaria transmission and for controlling other mosquito vectors of human diseases. The recent release of the DNA sequence of the A. gambiae genome has been a major achievement that should make possible rapid progress in molecular studies of the function of gene products in this mosquito. This proposal for an Investigator-Initiated Small Research Grant is to initiate pilot studies on the biochemistry of two groups of proteins in An. gambiae: serpins and laccases. Serpins are serine protease inhibitors, which have potential to regulate insect immune responses. However, their functions in mosquitoes have not yet been defined. Laccases are copper oxidases that can oxidize diphenols as well as other types of substrates. Laccases may function in insect cuticle sclerotization or immunity, but they have been the subject of little previous biochemical study. The aims of this project are to obtain full-length cDNA clones corresponding to the five laccase-like genes and a selected group of the 14 serpin genes from An. gambiae and to use these cDNAs as probes to study expression of the genes and for production of recombinant proteins for initiation of biochemical studies. These aims are intended to produce preliminary results to support future more extensive proposals on An. gambiae serpins and laccases. This project will be a start toward development of a new research area for the PI (mosquito biochemistry) that will build from his experience in biochemistry of other groups of insects.