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

这是美国国际和平研究所(哈佛大学埃雷尔·莱文博士)和以色列魏兹曼研究所的乔尔·斯塔万斯博士合作的研究提案。细菌细胞是由其膜内的一个隔室组成的，这往往导致假设细菌细胞是一个混合良好的均匀环境。然而，越来越多的证据表明，细菌细胞中的许多过程是有空间组织的，并且一些分子，包括某些基因的信使RNA(MRNAs)，表现出明显的非随机分布模式。这个项目解决了空间分布模式如何有助于和影响功能；它们如何被调节；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，并获得拟议项目的实验和理论方面的实践经验。这项合作为这个培训和一个高中生研究网络增加了一个国际维度。将使用先进的显微镜技术、分子系统生物学的实验方法和理论建模来揭示在拥挤的细胞环境中生物控制动力学的基本原理。将讨论以下具体问题：1)作为sRNAs靶标的转录本的定位，以及sRNAs调控这种定位的方式；2)sRNA-靶相互作用在依赖于定位的sRNA调控中的机制作用；3)亚细胞定位对网络基序调控特性的影响。这些信息将促进基因调控预测模型的发展，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).