Understanding Regulatory RNA-protein Networks to Control Cellular Metabolism

智能控制细胞代谢是现代细胞和生物分子工程的主要目标之一。最近发现的作为调节器的非编码RNA导致了一类全新的代谢调节，它已经在合成生物学和代谢工程中找到了重要的位置。然而，调控RNA与整个蛋白质网络相互作用以同时调节多条代谢途径以响应外部输入的机制尚不清楚。该项目旨在应用一种新的方法，利用最近开发的在体分子表征工具和定量建模方法来：(1)在应激-响应机制的背景下研究调节RNA-蛋白质相互作用所使用的基本分子特征，以及(2)将实验数据转化为定量动力学模型，该模型捕捉外部应激、代谢变化和分子相互作用之间的相互作用。这项研究将进一步加深我们对分子调节剂在体内和自然细胞网络中如何发挥作用的理解，有助于更全面地了解细胞行为。更广泛的影响这些研究将产生更广泛的影响，通过利用RNA-蛋白质调节的独特模式为细胞工程提供新的手段和方法。这项研究的结果有望在提高经济上有意义的生物技术过程中的微生物生产力方面找到广泛的应用。此外，建立一个通用的跨学科平台来研究RNA调节因子在体内和整个代谢网络中的作用，将对更广泛的研究界具有价值。此外，该项目还将通过“培养未来科学家”计划，向低收入、代表性不足的社区提供更广泛的外展服务。该计划将努力提高初中生和高中生及其家长对工程和科学可以解决和解决的社会问题的认识。

Intellectual meritControl of cellular metabolisms is one of the main objectives of modern cellular and biomolecular engineering. The recent discovery of noncoding RNAs as regulators has led to an entire new class of metabolic regulation that has already found a significant place in synthetic biology and metabolic engineering. However, the mechanisms by which regulatory RNAs interact with entire protein networks to simultaneously regulate multiple metabolic pathways in response to external inputs are less understood. This project aims to apply a novel method that employs recently developed in vivo molecular characterization tools and quantitative modeling approaches towards: (1) investigating basic molecular features used by regulatory RNA-protein interactions in the context of stress-response mechanisms, and (2) translating experimental data into quantitative kinetic models that capture the interplay between external stresses, metabolic changes, and molecular interactions. This research will result in furthering our understanding of how molecular regulators function in vivo and in the context of natural cellular networks, contributing to a more complete picture of cell behavior.Broader impactsThese studies will have the broader impact of providing new means and approaches for cellular engineering through exploiting the unique modes of RNA-protein regulation. The results of this research are expected to find broad applications in improving the productivity of microorganisms in economically interesting biotechnology processes. Furthermore, establishing a general interdisciplinary platform for studying how RNA regulators function in vivo and in the context of entire metabolic networks will be of value to the broader research community. In addition, this project will support broader outreach efforts to a low-income underrepresented community through the "Raising Future Scientists" program. This program will seek to increase awareness among middle school and high school students, and also their parents, about the societal problems that engineering and science can address and solve.