CHEMICAL & GENETIC APPROACHES TO DEFINE CELL ACTIVATION

已经出现了复杂的策略来调节所有病原体中关键的营养/寄生转变，在许多情况下，这种调节是由双组分调节系统提供的。植物病原体农杆菌的VirA/VirG系统是几种不同外部信号输入的关键整合器模型，这些信号输入是致病所必需的。它是唯一已知输入信号的系统，并且存在信号感知模型。此外，操纵基因组的遗传和分子工具已经到位，使得控制vir基因表达的因素能够在致病生物本身中轻松安全地控制。为了抓住这个机会，我们提出了一个实验计划，使我们能够测试一个分子模型的信号感知，整合和传输的致病信号。该方法利用了广泛的化学、物理和遗传方法，这些方法利用了两个不同机构不同实验室的可用资源。这些研究的结果将使我们能够确定信号输入如何在双组分响应调节器中被识别、整合和转导。此外，这种特定的信号系统调节了唯一已知的王国间基因转移的天然载体，了解这种机制已经并将继续扩大其在生物技术中的应用范围。

Sophisticated strategies have emerged to regulated the critical vegetative/parasitic transition in all pathogens, and in many cases, this regulation is provided by two-component regulatory system. The VirA/VirG system of the plant pathogen Agrobacterium tumefaciens is the model of a critical integrator of several different external signal inputs necessary for the commitment to pathogenesis. It is the only system for which the input signal is known and a model for signal perception exists. Moreover, the genetic and molecular tools to manipulate the genome are in place, allowing the factors that control vir gene expression to be easily and safely controlled in the pathogenetic organism itself. To seize this opportunity, we propose an experimental plan to allows us to test a molecular model for signal perception, integration, and transmission in pathogenetic signaling. The approach utilizes a wide range of chemical, physical, and genetic methods that exploit the resources available in different laboratories at two distinct institutions The results of these studies will place us in the position to determine how signal input is recognized, integrated, and transduced in two-component response regulators. In addition, this specific signaling system regulates the only known natural vector for inter-Kingdom gene transfer and understanding this mechanism has already and will continue to widen the range of its use in biotechnology.