Agricultural insect pest control: combining genetics, resistance management and dynamics

公众和消费者越来越希望看到使用更可持续的方法来控制害虫，人们普遍关注促进农业生态系统的可持续性和生物多样性。小菜蛾（Diamondback moth， DBM）是一种世界性的十字花科植物（如西兰花、卷心菜）害虫，通过管理成本和作物损害，每年造成40亿美元的经济损失。DBM已经进化出对所有已知种类的合成化学杀虫剂和至少两种基于Bt的苏云金芽孢杆菌的生物杀虫剂的抗性。Bt毒素通常对特定昆虫目（如鳞翅目）具有特异性作用，具有无与伦比的环境安全性，并已被广泛应用于转基因作物。对Bt毒素的抗性演变是对这一关键生物农药可持续开发的真正挑战。DBM不仅在田间多次进化出对Bt的抗性，而且还是一种验证进化理论的实验室系统。我们的行业合作伙伴Oxitec有限公司（牛津大学的衍生公司）正在开拓基因工程“不育”昆虫，以抑制农业或公共卫生害虫的数量。被释放的“RIDL”雄性昆虫在野外找到配偶，它们的后代继承了一种阻止它们发育成成年的基因结构。我们的理论工作预测，雌性特有的版本不仅会减少昆虫数量（雌性死亡，因此产卵的雌性更少），而且还有助于稀释种群中的任何抗性（雄性从释放的雄性那里继承bt易感等位基因）。我们的跨学科研究项目汇集了DBM-Bt系统的生态学和进化专家以及世界领先的生物技术专家，探索昆虫对生物农药的抗性管理以及与遗传昆虫控制的相互作用。除了Oxitec的原型外，还将开发新的DBM RIDL菌株，并将分阶段进行一系列实验，研究它们的生物学、遗传性状以及抑制DBM种群和管理Bt抗性的性能。主要性能性状包括雄性交配竞争力、与野生型雄性的精子竞争、寿命、传播、寻找配偶的能力和大规模饲养的适用性。从小型实验室笼子实验到模拟（野外笼子）和实际野外条件下的实验，这些将在越来越详细和现实的水平上进行分析，逐步确定并优先考虑最合适的菌株。我们将进行一系列竞争和选择实验，探讨RIDL雄性释放对DBM对Bt生物农药抗性进化的影响。这些实验将纳入现有抗性管理策略的关键特征，例如无Bt避难所，提供Bt易感基因来源和Bt饲料（这是目前管理Bt作物抗性措施的一个关键特征），具有非均匀空间结构和各种生态条件的种群，以及不同毒素的混合物（在喷雾处理中使用多种毒素并将其改造到某些植物中）。这些实验将为有关耐药性演变的理论预测提供直接测试，并提供有关系统动力学的信息，为进一步的数学模型的制定和参数化提供信息。我们的实证实验将得到一系列新颖数学模型的支持，以更全面地了解生物农药与遗传虫害防治相结合的综合虫害管理方法的生物经济学。我们将探讨以生物为基础的农业害虫（如DBM）综合管理的潜在成本效益和政策选择。

The public and consumers increasingly want to see more sustainable methods used to control pests and there is general concern to promote sustainability and biodiversity in agricultural ecosystems.Diamondback moth (DBM) is a major worldwide pest of brassicas (e.g. broccoli, cabbage) causing economic losses of $4-5bn annually through management costs and crop damage. DBM has evolved resistance to all known classes of synthetic chemical insecticides and to at least two bio-pesticides based on Bt, Bacillus thuringiensis. Bt toxins typically have specific action against particular insect Orders (e.g. Lepidoptera), have unparalleled environmental safety and have been widely engineered into transgenic crops. The evolution of resistance to Bt toxins is a real challenge to the sustainable exploitation of this key bio-pesticide. DBM has not only evolved resistance to Bt many times in the field, but is also a proven laboratory system for testing evolutionary theory.Our industry partner, Oxitec Ltd (an Oxford spin-out), is pioneering genetically engineered "sterile" insects to suppress populations of agricultural or public health pests. Released "RIDL" male insects find mates in the wild and their offspring inherit a genetic construct that prevents them developing to adulthood. Our theoretical work predicts that a female-specific version will not only reduce insect numbers (daughters die so there are fewer females to lay eggs) but also help dilute any resistance in the population (sons inherit Bt-susceptible alleles from released males).Our cross-disciplinary research project brings together experts in ecology and evolution of the DBM-Bt system and world-leading biotechnologists to explore the management of insect resistance to bio-pesticides and the interplay with genetic insect control.Novel RIDL strains of DBM will be developed, in addition to Oxitec's prototypes, and a phased series of experiments will be conducted on their biology, genetic traits, and performance for suppressing DBM populations and managing resistance to Bt. Key performance traits include male mating competitiveness, sperm competition with wild-type males, longevity, dispersal, the ability to find mates and suitability for mass-rearing. These will be analysed at increasing levels of detail and realism, from small laboratory cage experiments to experiments in simulated (field cage) and actual field conditions, progressively identifying and prioritizing the most suitable strains.We will perform a series of experiments involving competition and selection to explore the effect of RIDL male releases on the evolution of DBM resistance to Bt bio-pesticides. The experiments will incorporate key features of existing resistance management strategies, such as Bt-free refuges to provide a source of Bt-susceptible genes alongside Bt diet (this is a key feature of current measures to manage resistance to Bt crops), populations with non-homogeneous spatial structure and various ecological conditions, and mixtures of different toxins (multiple toxins are used in spray treatments and engineered into some plants). These experiments will provide direct tests of theoretical predictions about the evolution of resistance and provide information about the system's dynamics to inform the formulation and parameterization of further mathematical models.Our empirical experiments will be supported by a range of novel mathematical models to gain a fuller understanding of the bio-economics of integrated pest management approaches combining bio-pesticides with genetic pest control. We will explore the potential cost-effectiveness and policy options for integrated biologically-based management of agricultural pests such as DBM.