CAREER: Exploiting genetic compensation to define mechanisms of juvenile hormone homeostasis

This CAREER project seeks to determine how levels of isoprene-based juvenile hormones are regulated by homeostatic feedback mechanisms, to identify factors required for juvenile hormone synthesis, and to apply this new knowledge toward control of agricultural insect pests. The precise control of hormones is essential for development, reproduction, behavior, and physiology of animals. In arthropods, these processes are controlled by juvenile hormones. The potent effects of juvenile hormone on development have been leveraged around the world to control insects that threaten plants, animals, and humans. Indeed, juvenile hormone mimics are used as insect growth regulators and more recently to increase the efficacy of sterile insect technologies. Despite the importance to health, agriculture, and the economy, fundamental insights into juvenile hormone biology are lacking due to extensive genetic redundancies and robust, yet poorly understood, feedback. This research will use the experimentally tractable fruit fly, Drosophila melanogaster, as an insect model to identify mechanisms of endogenous juvenile hormone homeostasis and resistance to juvenile hormone-based insect growth regulators. Identification of such mechanisms will inform biotechnology efforts currently underway to combat invasive insect species that impact the agricultural and biomedical sectors, national defense, and economy of the United States. This research will be done primarily at the University of Texas at San Antonio, by graduate and undergraduate students, including those enrolled in course-based undergraduate research. By integrating the research objectives with course-based undergraduate research and a Teacher Development Workshop, this work will provide undergraduate students with opportunities to engage in publishable biology research and K-12 science teachers with a biology module focused on invasive insects that directly impact the economy in South Texas. By connecting the project’s research goals with locally relevant economic impacts of invasive insects, this work will increase public scientific literacy and engagement, as well as competitiveness of the U.S. workforce in several sectors, including fundamental biological research, applied entomology, and agricultural biotechnology. This integrated research and educational project will couple extensive preliminary data on compensatory feedback within the juvenile hormone axis with a broadly conserved phenomenon of paralog upregulation to 1) define the transcriptional mechanisms of juvenile hormone feedback, 2) identify long-elusive proteins that regulate juvenile hormone metabolism, and 3) elucidate the feedback mechanisms that confer resistance to juvenile hormone mimics. These goals will be accomplished through a combination of molecular biology approaches, transcriptomics, genetic screens and biochemical assays. Completion of these objectives will provide academic researchers with additional genetic tools to manipulate juvenile hormone in vivo and provide industry scientists with biomarkers for emerging resistance to juvenile hormone-based insect growth regulators, thus fostering cross-sector collaborations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2541219 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT,01003031DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Lacy Barton | Institution: University of Texas at San Antonio, SAN ANTONIO, TX | Award Amount: $714,526 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2541219 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2541219.html