CAREER: Exploring the windows of selection for insecticide resistance evolution

对除草剂、杀真菌剂、杀虫剂、抗微生物剂、抗病毒药和抗癌药物的抗性的演变是一个重大的全球性挑战。为了制定有效的抗性管理策略，重要的是要了解不同的组合和浓度如何影响抗性的演变。这一知识可用于了解在不同暴露下或随着浓度随时间推移而减弱时，抗性演变如何变化。该项目的目的是通过将蚊子的杀虫剂抗性进化作为一个模型系统来填补这方面知识的差距。通过测量不同杀虫剂组合和浓度下作用于抗性和敏感蚊子的选择，将建立杀虫剂抗性进化的综合进化框架。此外，由于耐药性演变等复杂问题预计在可预见的未来将在全球范围内继续存在，因此迫切需要多样化的劳动力。该项目将为本科生和K-12学生围绕杀虫剂抗性进化开发研究和基于调查的经验。重点将放在学生从较低的社会经济或代表性不足的背景，以加强学生参与科学和接触学生的多元化的过程中的科学。耐药进化是由增加的生存抗性生物体在异生环境（环境与农药，抗生素，或其他“杀”）相对于敏感的生物体。选择窗口是观察到不同死亡率的浓度范围，并被用作确定选择发生的浓度的框架，或确定在不可避免地减弱的浓度下该窗口打开的时间长度。在这一框架中经常缺少的是种间竞争在两种菌株生存的浓度下的作用：在低浓度下。研究目的是检验选择窗口包含一个或多个竞争子窗口，然后是负选择窗口的假设。具体目标是：1）建立选择窗内不同剂量下抗药性等位基因的选择系数，2）确定与杀虫剂抗性等位基因相关的适合度成本的大小，以及3）该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准。

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.