Cis-regulatory element discovery in a sequenced mosquito genome

Indiana University Indianapolis, Indianapolis IN

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Abstract

? 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.