Transcription and Translation Dynamics in Live Escherichia coli

该项目使用最先进的活细胞显微镜来揭示控制细菌细胞生长速度的基本机制。 由此产生的对细菌细胞内部运作的更好理解不仅推进了重要的基础知识，而且可能最终导致细菌感染的新疗法。 从事这项跨学科工作的研究生将学习细菌遗传学和生物化学，并在生物物理测量和数据分析方面发展强大的定量技能。基因组信息从DNA到蛋白质的转移通过mRNA中间体发生。 在细菌细胞中，有效的细胞生长需要RNA合成（转录）和蛋白质合成（翻译）过程的紧密耦合。 然而，控制转录和翻译如何在时间和空间上协调的机制尚不清楚。 最近开发的荧光显微镜方法使得有可能跟踪负责活大肠杆菌细胞中的转录（RNA聚合酶）和翻译（核糖体）的分子。 这项研究将利用这项新技术来确定基因、RNA聚合酶分子和核糖体如何在细胞质内分布以及它们如何随时间移动，空间精度约为30纳米，时间分辨率约为10毫秒。 这些数据将用于生成新的生物物理和生物化学模型，以了解转录和翻译如何同步以促进细菌的快速生长。 此外，这些结果预计将为三维空间和时间组织如何优化不同生化过程的细胞输出提供可推广的见解。

This project uses state-of-the-art live cell microscopy to unravel fundamental mechanisms that control how quickly bacterial cells grow. The resulting better understanding of the inner workings of bacterial cells not only advances important basic knowledge but may also eventually lead to novel therapies for bacterial infections. Graduate students engaged in this interdisciplinary work will learn bacterial genetics and biochemistry and develop strong quantitative skills in biophysical measurement and data analysis. The transfer of genomic information from DNA to protein occurs via an mRNA intermediate. In bacterial cells, efficient cell growth requires close coupling of the processes of RNA synthesis (transcription) and protein synthesis (translation). However, the mechanisms that control how transcription and translation are coordinated in time and space are not clear. Recently developed fluorescence microscopy methods have made it possible to track the molecules responsible for transcription (RNA polymerase) and translation (ribosome) in live Escherichia coli cells. This research will take advantage of this new technology to determine how genes, RNA polymerase molecules, and ribosomes are distributed within the cytoplasm and how they move over time, with spatial precision of about 30 nanometers and time resolution of about 10 milliseconds. The data will be used to generate new biophysical and biochemical models of how transcription and translation are synchronized to facilitate rapid bacterial growth. Moreover, the results are anticipated to provide generalizable insights into how three-dimensional spatial and temporal organization can optimize cellular outputs from distinct biochemical processes.