Regulatory element discovery in Anopheles gambiae

转录增强子的鉴定--调控基因所需的非编码调控序列 表达-对于理解疾病媒介的基本生物学，特别是对于 开发生物技术手段，操纵其生命周期，以便对其进行管理和控制。然而，在这方面， 在媒介昆虫，包括主要的疟疾媒介中，很少发现这样的调节序列 冈比亚按蚊，尽管有完整的基因组测序。调查人员已 开发了在果蝇中发现有效的计算增强子的方法，并证明， 广泛的果蝇增强子数据可以用来在其他领域发现增强子。 像蚊子、甲虫、蜜蜂和黄蜂这样多种多样的昆虫。此R21应用程序的目标是使用此 方法来发现和验证在体内增强相关的载体生物学和昆虫生物防治中， 按蚊冈比亚。这样做的基本原理是，鉴定顺式调节序列， 在研究和控制蚊子疾病媒介方面取得了重要进展，但更深层次的 需要收集蚊子增强剂。这项拟议中的研究有可能提供大量 已知或预测的增强子，其中很少或根本不存在。这是一项探索性的、新颖的研究， 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生成高置信度的增强子预测。冈比亚; 和（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 丰富的现有果蝇顺式调控数据，以有效地预测增强子超过大的进化 距离在一个重要的载体物种，有基因组序列，但很少的功能数据。的 建议的研究是重要的，因为目前没有其他方法可用于快速，有效， 在已经测序的重要载体物种中发现具有成本效益的增强子。如果成功，它将 证明有能力注释所有昆虫疾病载体的调控基因组，因为它们变得 测序，而不需要广泛的新的基因组规模的实验数据。这些结果将 一个重要的积极影响，通过提高能力，了解和操纵生物学的安。冈比亚按蚊 和其他病媒物种，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.