Regulatory element discovery in Anopheles gambiae

识别转录增强子--调控基因所需的非编码调控序列 表达-对于理解病媒的基本生物学，特别是对 开发生物技术手段，操纵它们的生命周期，对其进行管理和控制。然而， 对于媒介昆虫，包括主要的疟疾媒介昆虫，几乎没有发现这样的调控序列。 冈比亚按蚊，尽管有完全测序的基因组。调查人员已经 开发了在果蝇中发现有效计算增强子的方法，并证明了 大量的果蝇增强子数据可以被用来在其他 种类繁多的昆虫，如蚊子、甲虫、蜜蜂和黄蜂。这个R21应用程序的目标是使用以下内容 发现和验证与病媒生物和昆虫生物防治相关的体内增强剂的方法 疟疾蚊子。冈比亚亚目。其基本原理是识别顺式调节序列具有 在蚊子病媒的研究和控制方面取得了重要进展，但深入得多 收集蚊子增强剂是必要的。这项拟议的研究有可能提供大量的数据 已知或预测的增强剂，而现在几乎不存在。这是一项探索性的、新颖的研究，将打破 在蚊子基因组学和遗传学领域的新领域，因此非常适合R21赠款 机制。有两个具体的目标：(1)为AN生成高置信度增强器预测。冈比亚亚纲； 以及(2)在转基因蚊子中验证增强子预测。这种方法是创新的，因为它利用了 现有果蝇顺式调控数据的丰富，可有效预测增强剂对大型进化的影响 有基因组序列但功能数据很少的重要媒介物种的距离。这个 建议的研究具有重要意义，因为目前还没有其他方法可以快速、高效和 在已经测序的重要媒介物种中发现具有成本效益的增强子。如果成功，它将 有能力对所有昆虫疾病媒介的调控基因组进行注释 测序，而不需要大量新的基因组规模的实验数据。这些结果将会有 通过提高理解和操纵细菌生物学的能力，产生了重要的积极影响。冈比亚亚纲 和其他媒介物种，以改善其管理和控制。

Identifying transcriptional enhancers—the non-coding regulatory sequences required for regulating gene expression—is critical both for understanding the basic biology of disease vectors and especially for developing biotechnological means of manipulating their life cycles for their management and control. However, few such regulatory sequences have been identified for vector insects, including the major malaria vector Anopheles gambiae, despite the availability of completely sequenced genomes. The investigators have developed methods for effective computational enhancer discovery in Drosophila and have demonstrated that Drosophila enhancer data, which are extensive, can be leveraged to enable enhancer discovery in other insects as diverse as mosquitoes, beetles, bees, and wasps. The objective of this R21 application is to use this approach to discover and validate in vivo enhancers relevant to vector biology and insect biocontrol in the malaria mosquito An. gambiae. The rationale for this is that identification of cis-regulatory sequences has provided important advances in the study and control of mosquito disease vectors, but a much deeper collection of mosquito enhancers is needed. The proposed research has the potential to provide large numbers of known or predicted enhancers where few or none now exist. It is an exploratory, novel study that will break new ground in the field of mosquito genomics and genetics and is therefore ideally suited for the R21 grant mechanism. There are two specific aims: (1) Generate high-confidence enhancer predictions for An. gambiae; and (2) Validate the enhancer predictions in transgenic mosquitoes. This approach is innovative as it leverages the wealth of existing Drosophila cis-regulatory data to effectively predict enhancers over large evolutionary distances in an important vector species for which there is genome sequence but little functional data. The proposed research is significant because there is currently no other method available for rapid, efficient, and cost-effective enhancer discovery in already-sequenced, important vector species. If successful, it will demonstrate an ability to annotate the regulatory genomes of all insect disease vectors as they become sequenced without requiring extensive new genome-scale experimental data for each. These results will have an important positive impact through improved ability to understand and manipulate the biology of An. gambiae and other vector species to improve their management and control.