Protein interaction topologies regulating virus transmission by insect vectors

昆虫传播的病毒在全球范围内对包括人类在内的动植物健康构成最大威胁之一。病毒使用蛋白质作为工具，以确保自己通过昆虫传播和在宿主中感染。病毒已经微调了它们与宿主和媒介蛋白的相互作用，以便在宿主内部和宿主之间移动。这里使用术语拓扑来表示蛋白质及其相互作用的结构和表面特征。研究人员将使用蛋白质相互作用报告程序，这是一项将化学交联和质谱学结合在一起的创新技术，以可视化涉及病毒传播和感染的蛋白质复合体的定量和结构信息。对社会的好处包括开发新的策略，扰乱病毒在宿主内部和之间的传播。几乎没有开发出有效的控制策略来阻止任何昆虫传播病毒的传播。大多数对环境和人类健康都有负面影响，而且是不可持续的。这个项目处于化学和生物的交界处。蛋白质相互作用报告是一项尖端技术，它可能会改变我们对病毒如何感染昆虫并通过昆虫传播的理解。研究人员已经发现的几个新的蛋白质拓扑信息的例子突出了这种协同方法的力量，进一步了解了涉及昆虫传播病毒的分子途径、拓扑和相互作用，但远远超出了传统方法的界限。调查人员将为生物和化学方面的博士后助理和本科生提供高级培训，重点是纳入来自代表性不足群体的受训人员。他们还将为希望将质谱学纳入他们的教学和研究计划的科学家举办一次拨款撰写研讨会。

Insect-vectored viruses pose one of the greatest threats to plant and animal, including human, health on a global scale. Viruses use proteins as tools to ensure their own transmission by insects and infection in hosts. Viruses have finely tuned their interactions with host and vector proteins for movement within and between hosts. The term topology is used here to indicate structural and surface features of proteins and their interactions. The investigators will use Protein Interaction Reporter, an innovative technology that couples chemical cross-linking and mass spectrometry, to visualize quantitative and structural information about protein complexes involved in virus transmission and infection. The benefits to society include the development of novel strategies that disrupt virus movement within and between hosts. Few effective control strategies have been developed to thwart transmission of any insect-transmitted virus. Most have negative impacts on the environment and human health and are unsustainable. This project is at the interface of chemistry and biology. Protein Interaction Reporter is a cutting-edge technology that will potentially transform our understanding of how viruses infect and are transmitted by insects. Several examples of novel protein topological information the investigators have already discovered highlight the power of this synergistic approach to further fundamental understanding of molecular pathways, topologies, and interactions involved in virus transmission by insects, yet are far beyond the boundaries of conventional approaches. The investigators will provide advanced training to postdoctoral associates and undergraduate students in biology and chemistry with an emphasis on including trainees from underrepresented groups. They will also hold a grant-writing workshop for scientists who wish to integrate mass spectrometry into their teaching and research programs.