NSF/MCB-BSF: Sub-cellular Localization and Small RNA Regulation of the Outer Membrane

这是美国PI（哈佛大学Erel Levine博士）和以色列魏茨曼研究所Joel Stavans博士之间的合作研究计划。细菌细胞由其膜内的单个隔室组成，这通常导致假设细菌细胞是充分混合的均匀环境。然而，已经积累的证据表明，细菌细胞中的许多过程是空间组织的，并且一些分子，包括一些基因的信使RNA（mRNA），表现出明显的非随机分布模式。该项目涉及空间分布模式如何有助于和影响功能;它们如何受到调节;以及分布模式如何影响活细菌中分子之间的相互作用。本科生和研究生将接受培训，并在拟议项目的实验和理论方面获得实践经验。该合作为该培训以及高中生研究网络增加了国际层面。将使用先进的显微技术，分子系统生物学的实验方法和理论建模来揭示细胞拥挤环境中生物控制动力学的基本原理。 以下具体问题将得到解决：1）的转录本的定位，是目标的sRNA，和这种定位的方式是由sRNA调制2）的机制作用的sRNA靶相互作用的定位依赖的sRNA调节和3）的影响，亚细胞定位的网络基序的调节特性。这些信息将促进基因调控的预测模型的发展，这些模型可以解释细胞行为并指导合成电路的设计。该奖项由分子和细胞生物科学部和物理学部（生命系统物理学）共同支持。

This is a collaborative research proposal between the US PI (Dr Erel Levine, Harvard University) and Dr Joel Stavans of the Weizmann Institute, Israel. The bacterial cell is composed of a single compartment within its membrane, which often leads to the assumption that the bacterial cell is a well-mixed homogeneous environment. However, evidence has accumulated that many processes in the bacterial cell are spatially organized, and that some molecules, including messenger RNAs (mRNAs) of some genes, exhibit clear patterns of distribution that are non-random. This project addresses how patterns of spatial distribution can contribute to and affect function; how they are regulated; and how distribution patterns affect interactions between molecules in the living bacterium. Undergraduate and graduate students will be trained and gain hands-on experience in both the experimental and theoretical aspects of the proposed project. The collaboration adds an international dimension to this training as well as to a high-school student research network.Fundamental principles of the dynamics of biological control in the crowded environment of the cell will be uncovered using advanced microcopy techniques, experimental methods of molecular systems biology, and theoretical modeling. The following specific issues will be addressed: 1) the localization of transcripts that are targets of sRNAs, and the manner in which this localization is modulated by sRNAs 2) the mechanistic roles of sRNA-target interactions in localization-dependent sRNA regulation and 3) the implications of sub-cellular localization for the regulatory properties of network motifs. This information will facilitate the development of predictive models of gene regulation that can explain cellular behaviors and direct the design of synthetic circuits.This award is supported jointly by the Division of Molecular and Cellular Biosciences and the Division of Physics (Physics of Living Systems).