CAREER: Multi-input Multi-output Cellular Control: Bacterial Type III Secretion as a Model System

本研究的目的是开发计算和实验方法来量化网络如何集成来自多个传感器的输入并在多个细胞响应中进行选择。由于激活传感器的刺激是未知的或在培养中难以控制，因此量化信号是如何整合的通常是具有挑战性的。在Aim 1中，嵌合传感器将被构建，其中可以使用小分子诱导剂改变激酶活性。多个嵌合体将用于确定监管网络执行的底层逻辑操作。在目标2中，将开发一种通用的方法来确定细胞群体如何在多个共调节反应之间分化。这些方法将作为多输入多输出控制的模型系统，应用于沙门氏菌控制III型分泌的调控网络。将开发两个教育项目，培训高中生、本科生和研究生理解和设计复杂生物系统的方法。首先，将设计一门新的核心研究生课程，教授从传输现象、动力学、非线性动力学到生物学问题的技术。其次，将组织包括高中生在内的多元化学生团队参加校际基因工程竞赛（iGEM），其目标是设计和构建合成生物体。

Voigt0547637The objective of this research is to develop computational and experimental methods to quantify how a network integrates inputs from multiple sensors and chooses amongst multiple cellular responses. It is often challenging to quantify how signals are integrated because the stimulus that activates a sensor is unknown or difficult to control in culture. In Aim 1, chimeric sensors will be constructed where the kinase activity can be varied using small molecule inducers. Multiple chimeras will be used to determine the underlying logic operations performed by a regulatory network. In Aim 2, a general methodology will be developed to determine how a cell population bifurcates between multiple co-regulated responses. These methods will be applied to the Salmonella regulatory network controlling type III secretion as a model system of multi-input multi-output control. Two educational programs will be developed to train high school, undergraduate, and graduate students in methods to understand and engineer complex biological systems. First, a new core graduate course will be designed to teach techniques from transport phenomena, kinetics, and non-linear dynamics to problems in biology. Second, a diverse student team, including high school students, will be organized to compete in an intercollegiate genetic engineering competition (iGEM), the goal of which is to design and build a synthetic organism.