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.
The proposed research program will examine the biology of Aedes aegypti, the mosquito vector for dengue, which threatens more than 2.5 billion people in the tropics and is responsible for 50 million illnesses resulting in ~22,000 deaths annually. This study will generate a toolkit of gene drivers for manipulation of gene expression in A. aegypti that could be extended to additional vector insect species. This investigation aims to change the framework in which vector biologists pursue science and promote the elucidation of novel approaches to target human disease vector insects.
| Behura, Susanta K; Sarro, Joseph; Li, Ping et al. (2016) High-throughput cis-regulatory element discovery in the vector mosquito Aedes aegypti. BMC Genomics 17:341 |
| Duman-Scheel, Molly; Syed, Zainulabeuddin (2015) Developmental neurogenetics of sexual dimorphism in Aedes aegypti. Front Ecol Evol 3: |
