在同一种作物中转入针对同一种害虫的两个或多个不同类型的Bt基因，对靶标害虫实现“饱和杀死”，从而可以延缓抗性发展，该抗性治理策略称为“基因聚合策略”。靶标害虫可以进化出交互抗性适应此策略，因此，弄清靶标害虫通过何种机制形成稳定遗传的交互抗性来适应多基因Bt作物是成功实施基因聚合策略的关键。为了探究这一重要科学问题，本项目将在建立室内筛选的以及田间分离的多个棉铃虫对Cry1Ac和Cry2Ab交互抗性品系的基础上，以抗性相关基因的高通量筛选为切入点，通过基因定位、转录组和蛋白组数据关联分析和毒素受体互作分析等技术手段揭示Bt毒素的毒理学机制和交互抗性机理，阐明棉铃虫对不同Bt毒素交互抗性的分子遗传机制。项目成果不仅可以提出Bt作用机制及交互抗性机理的新模式，同时还为Bt基因聚合抗虫作物选育中Bt基因的科学搭配及靶标害虫抗性治理新策略的研发提供重要理论依据。

Pyramided Bt crops produce two or more distinct Bt toxins that kill the same insect pest. The pyramiding strategy for Bt resistance management is expected to delay resistance evolution on the basis of “redundant killing”, which means the target insects will be killed twice. Target pests are possible to adapt to the pyramided Bt crops through evolution of cross-resistance to two or more Bt toxins, so it is very crucial to understand which mechanisms and pathways of cross-resistance the target pest will evolve to cope with multiple Bt toxins. To address this key scientific question, molecular mechanisms of cross-resistance to Bt Cry toxins Cry1Ac and Cry2Ab will be investigated in several laboratory-selected and field-derived resistant strains of Helicoverpa armigera. Multiple approaches, including positional cloning, association analysis of transcriptomic and proteomic data and interaction analysis between Bt toxins and midgut receptors, will be employed to elucidate genetic diversity and the underlying mechanisms of cross-resistance to Cry1Ac and Cry2Ab in H. armigera. Our results are not only expected to improve present models for mode of action of and resistance mechanisms to Bt Cry toxins, but also to provide the theoretical basis for both optimizing Bt gene pyramiding and developing new tactics for Bt resistance management in target insect pests in future.