CAREER: Exploring the windows of selection for insecticide resistance evolution

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The evolution of resistance against herbicides, fungicides, pesticides, antimicrobials, antivirals, and anticancer drugs is a major global challenge. To develop effective resistance management strategies, it is important to understand how the different combinations and concentrations affect the evolution of resistance. This knowledge could be used to understand how resistance evolution changes under varying exposures or as concentrations wane over time. The aim of this project is to fill the gap in this knowledge by focusing on insecticide resistance evolution in mosquitoes as a model system. A comprehensive evolutionary framework of insecticide resistance evolution will be developed by measuring the selection acting upon resistant and susceptible mosquitoes under different insecticide combinations and concentrations. Furthermore, with problems as complex as resistance evolution that is predicted to continue globally in the foreseeable future, a diverse workforce is urgently needed. This project will develop research and inquiry-based experiences for undergraduate and K-12 students around insecticide resistance evolution. The focus will be on students from lower socio-economic or underrepresented backgrounds to bolster student engagement in science and expose a diverse group of students to the process of science.Resistance evolution is driven by increased survival of resistant organisms in a xenobiotic environment (an environment with pesticides, antibiotics, or other "-cides") relative to susceptible organisms. The window of selection is the range of concentrations at which differential mortality is observed and is used as a framework to identify concentrations at which selection occurs, or identify the length of time this window is open at inevitably waning concentrations. Often missing from this framework is the role of interspecific competition at concentrations for which both strains survive: at low concentrations. The research goal is to test the hypothesis that the window of selection contains one or more sub-windows of competition, followed by a window of negative selection. The specific aims are to: 1) establish the selection coefficient of insecticide resistance alleles at different doses within the window of selection, 2) determine the magnitude of fitness costs associated with insecticide resistance alleles and 3) determine selection following various resistance management strategies using experimental and mathematical approaches.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.