Characterization and Expression of microRNA Genes in Anopheles gambiae

描述(申请人提供)：按蚊是疟疾的主要传播媒介。蚊子基因组学的最新发展以及从生物学其他领域收集到的范式转变的见解提供了令人兴奋的机会，极大地提高了我们对蚊子遗传学、生理学和行为的理解。蚊子生物学方面的新见解无疑将有助于制定防治疟疾和其他蚊媒疾病的新战略。这项研究的长期目标是确定冈比亚按蚊中一类名为microRNAs(MiRNAs)的新型基因调控分子的生物学功能，并通过研究miRNAs在与蚊子媒介能力密切相关的过程中的潜在作用，揭示控制媒介传播疾病的新方法。MiRNAs是大约22个核苷酸长的非编码RNA，通过与同源mRNA结合进行切割或翻译抑制来调节细胞基因的表达。在一些生物体中，microRNAs是胚胎发育、干细胞分裂、神经发生、造血细胞分化和细胞死亡的关键调控分子。它们还与病毒感染和癌症的控制有关。MiRNAs代表了媒介生物学中一个广阔而尚未开发的研究领域，它可以极大地扩展我们目前的知识，并为控制媒介传播的疾病提供潜在的靶点。我们最近通过比较An之间保守的非编码序列，鉴定了一些可能的蚊子特异性miRNA。冈比亚伊蚊和埃及伊蚊。我们的初步miRNA阵列数据表明，在一顿血餐后，几个miRNA的水平发生了显着变化。在这个探索性的R21项目中，我们将1)从An中鉴定出广泛的miRNAs。冈比亚，使用一种集成的双轨方法，涉及基因组规模的计算预测和直接克隆，2)确定在AN中miRNA表达的时空分布。冈比亚在血餐前后的不同时间点。我们将提供有关大量miRNAs的信息，这些信息将作为未来研究的基础。我们将专注于识别那些可能在不同组织中调节血粉触发过程的miRNAs。总体而言，拟议的研究将促进媒介研究，开始填补我们对蚊子生物学了解的一个重大空白，并有助于制定控制蚊媒传染病的新策略。

DESCRIPTION (provided by applicant): Anopheline mosquitoes constitute the primary vectors of malaria. Recent developments in mosquito genomics as well as paradigm-shifting insights gleaned from other areas of biology provide exciting opportunities to greatly enhance our understanding of mosquito genetics, physiology, and behavior. New insights in mosquito biology will undoubtedly facilitate the development of novel strategies to combat malaria and other mosquito-borne diseases. The long term objectives of the proposed research are to determine the biological functions of a novel class of gene regulatory molecules named microRNAs (miRNAs) in Anopheles gambiae and uncover novel approaches to control vector-borne diseases by investigating the potential roles of miRNAs in processes that are intimately linked to mosquito vectorial capacity. miRNAs are approximately 22 nucleotide long non-coding RNAs that modulate the expression of cellular genes by binding to cognate mRNA for cleavage or translational repression. In some organisms, microRNAs serve as key regulatory molecules during embryonic development, stem cell division, neurogenesis, haematopoietic cell differentiation, and cell death. They are also implicated in the control of viral infections and cancer. MiRNAs represent a vast and untapped research area in vector biology that could greatly expand our current knowledge and provide potential targets for control of vector-borne diseases. We have recently identified a number of putative mosquito-specific miRNA by comparing conserved non-coding sequences between An. gambiae and Aedes aegypti. Our preliminary miRNA array data indicate that the levels of several miRNAs change significantly after a blood meal. During this exploratory R21 project, we will 1) Identify a broad spectrum of miRNAs from An. gambiae, using an integrated, two-track approach that involves genome-scale computational prediction and direct cloning, 2) Determine the spatiotemporal profiles of miRNA expression in An. gambiae before and at different time points after a bloodmeal. We will provide information on a large repertoire of miRNAs that will serve as the foundation for future research. We will focus on identifying those miRNAs likely to regulate bloodmeal-triggered processes in different tissues. Overall, the proposed research will facilitate vector research by starting to fill a major gap in our understanding of mosquito biology and contribute to novel strategies to control mosquito-borne infectious diseases.