Protein interaction topologies regulating virus transmission by insect vectors

虫媒病毒是全球范围内动植物（包括人类）健康面临的最大威胁之一。病毒利用蛋白质作为工具，确保自己通过昆虫传播并感染宿主。病毒精细地调整了它们与宿主和载体蛋白的相互作用，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的结构和表面特征及其相互作用。研究人员将使用蛋白质相互作用报告（Protein Interaction Reporter），一种结合化学交联和质谱的创新技术，来可视化参与病毒传播和感染的蛋白质复合物的定量和结构信息。对社会的好处包括开发新的策略，破坏病毒在宿主内部和宿主之间的运动。很少有有效的控制策略来阻止任何昆虫传播的病毒的传播。大多数对环境和人类健康产生负面影响，是不可持续的。这个项目是化学和生物学的交叉点。蛋白质相互作用报告是一项尖端技术，可能会改变我们对病毒如何感染和通过昆虫传播的理解。研究人员已经发现了几个新的蛋白质拓扑信息的例子，突出了这种协同方法在进一步了解昆虫传播病毒的分子途径、拓扑结构和相互作用方面的力量，但远远超出了传统方法的界限。研究人员将为生物学和化学领域的博士后和本科生提供高级培训，重点是包括来自代表性不足群体的学员。他们还将为那些希望将质谱法整合到他们的教学和研究项目中的科学家举办一个拨款写作研讨会。

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.