Cis-regulatory element discovery in a sequenced mosquito genome

在测序的蚊子基因组中发现顺式调控元件

• 批准号: 8868422
• 负责人: Molly Duman Scheel
• 金额: $ 23.4万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8868422
• 关键词: Aedes; Animal Model; Biochemical; Biological Assay; Biology; Cessation of life; Communicable Diseases; Complex; Culicidae; DNA; DNA Sequence; Data Set; Dengue; Developed Countries; Development; Disease Outbreaks; Disease Vectors; Drosophila genus; Drosophila melanogaster; Elements; Epidemic; Epigenetic Process; Fat Body; Formaldehyde; Gene Expression; Gene Expression Profile; Generations; Genes; Genetic; Genetic Models; Genetic Research; Genetic study; Genome; Human; In Situ Hybridization; Insect Vectors; Insecta; Investigation; Knowledge; Midgut; Nucleosomes; Olfactory Pathways; Organism; Proteins; Regulation; Regulator Genes; Regulatory Element; Reporter; Research; Salivary Glands; Science; Technology; Testing; Time; Tissues; Transgenic Organisms; United States; Work; Yellow Fever; combat; design; developmental genetics; fly; high throughput screening; human disease; improved; in vivo; interest; killings; novel strategies; prevent; programs; public health relevance; reproductive; research and development; tool; vector; vector mosquito

 DESCRIPTION (provided by applicant): Vector mosquitoes inflict more human suffering than any other organism-and kill more than one million people each year. The mosquito genome projects have facilitated research in new facets of mosquito biology, including our functional genetic studies of development. Despite substantial progress in mosquito genetic research, regulation of mosquito gene expression is still poorly understood. For example, few cis-regulatory elements (CREs), DNA sequences that control gene expression, have been identified in mosquitoes. The resulting deficiency-a significant gap in the basic knowledge of mosquito genetics-has resulted in a lack of drivers to manipulate gene expression in selected tissues at specific times. Such tools, which have revolutionized research in genetic model organisms, would facilitate genetic studies and benefit all avenues of mosquito research. FAIRE-seq, formaldehyde-assisted isolation of regulatory elements paired with DNA sequencing, is emerging as a powerful new high-throughput tool for global CRE discovery. We recently performed a FAIRE-seq study in the dengue and yellow fever vector mosquito Aedes aegypti. These efforts resulted in identification of thousands of putative regulatory elements throughout the A. aegypti genome. The proposed investigation, which will test the hypothesis that these A. aegypti FAIRE DNA sequences function as CREs, includes a high throughput screen in transgenic insects that will examine the ability of hundreds of these elements to promote gene expression in vivo. In addition to validating the FAIRE data set, the screen has been designed to select for elements that have a high potential to drive gene expression in tissues of vector importance in multiple vector insect species. This research will generate a toolkit of gene drivers for mosquito research, promote use of FAIRE-seq in additional vector insect species, and encourage the study of mosquito gene regulatory networks. This work has the potential to change the framework in which vector biologists approach science.

 描述（由适用提供）：媒介蚊子造成的人类痛苦比其他任何生物体都要多，并且每年杀死超过一百万的人。蚊子基因组项目已经在蚊子生物学的新方面准备了研究，包括我们的发育功能遗传研究。尽管在蚊子遗传研究中取得了长足的进步，但蚊子基因表达的调节仍然鲜为人知。例如，在蚊子中已经鉴定出很少有顺式调节元件（CRE），即控制基因表达的DNA序列。由此产生的缺乏 - 在蚊子基因基本知识中的显着差距导致缺乏在选定时间操纵基因表达的驱动因素。这种彻底改变了遗传模型生物研究的工具将促进遗传研究并使蚊子研究的所有途径受益。甲醛辅助隔离与DNA测序配对的甲醛辅助隔离，正成为一种强大的新型高通量工具，可用于全球CRE发现。我们最近在粉丝和黄热病媒介埃德斯（Aedes Aedes Aedes）进行了一项公平的季节研究。这些努力导致确定了整个A. aegypti基因组中成千上万的推定调节元素。拟议的研究将检验以下假设：这些A. eegypti Faire DNA序列起CRE的作用，包括转基因昆虫中的高吞吐量筛选，这些筛查将研究这些元素在体内促进基因表达的能力。除了验证公平数据集外，该屏幕还设计为选择具有较高潜力的元素，这些元素可以在多种媒介昆虫物种中具有矢量重要性的基因表达。这项研究将生成基因驱动器的工具包 为了进行蚊子研究，请在其他载体昆虫物种中促进公平疾病的使用，并鼓励研究蚊子基因调节网络。这项工作有可能改变媒介生物学家对科学的框架。