NSF/MCB-BSF: Probing cellular surplus in single bacterial cells to understand concerted controls of cell growth and adaptation

细菌作为简单的生命有机体，可以在广泛的条件下生存和繁衍。在稳定条件下的快速生长和对新条件的快速适应都是增强细胞适应性的关键。这个项目的目标是了解定义细菌细胞非遗传适应的时间尺度的生理学基础。研究细菌细胞的基本生理学，如生长和适应，既需要定量实验，也需要细胞系统的整体建模。该项目的基础性、多学科和协作性使其适合于对本科生和研究生进行研究教育，并促进经过实验和建模培训的学生之间的互动。沿着这条线，将建立一个专注于代表性不足的少数群体的暑期本科课程，并将设立一个小型交流研究生项目，以加强两国在生物物理学研究方面的努力。该项目可能会在生物医学和生物技术领域得到应用。更好地了解细胞适应可以帮助揭示病原菌如何适应各种利基和抗生素，并在人体内产生耐受性。利用细胞适应可能会促进更强大的生物工业过程的发展。虽然控制细菌细胞在稳定条件下的生长速度已经被广泛研究，但在从一种条件切换到另一种条件时，是什么控制它们的适应时间在很大程度上仍不清楚。这个项目的主要策略是检验一个假设，即核心生物合成机器可能有盈余，这对保持稳定的增长并不是必需的，但有利于适应新的条件。该项目将通过对核心生物合成机器丰度的扰动，以及对单个大肠杆菌细胞生长和适应速度的影响的定量测量，来实验验证这一假设。该项目还将建立一个多尺度理论框架，将冗余引入核心生物合成网络，以解释实验观察结果并做出可检验的预测。该项目的预期结果可能通过控制细胞成分的丰度来揭示增长和适应的基本权衡战略。这一美国/以色列合作项目得到了美国国家科学基金会和以色列双国科学基金会的支持。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Bacteria as simple living organisms can survive and thrive in a broad range of conditions. Fast growth in steady conditions and rapid adaptation to new conditions are both essential for augmenting cell fitness. The goal of this project is to understand the physiological basis that defines the timescale of the non-genetic adaptation of bacterial cells. Studying the basic physiology of bacterial cells such as growth and adaptation requires both quantitative experiments and holistic modeling of the cellular system. The fundamental, multidisciplinary, and collaborative nature of this project makes it suitable for educating undergraduate and graduate students on research and fostering interactions between students trained in experiments and modeling. Along this line, a summer undergraduate program will be established focusing on underrepresented minority groups, and a mini-exchange graduate program will be set up to enhance binational efforts on biophysics research. This project could have biomedical and biotechnology applications. A better understanding of cellular adaptation can help unveil how pathogenic bacteria adapt to various niches and antibiotics and develop tolerance in the human body. Harnessing cellular adaptation may facilitate the development of more robust bio-industrial processes. While the control of the growth rate of bacterial cells in steady conditions has been extensively studied, what controls their adaptation time when switched from one condition to another is still largely unknown. The main strategy of this project is to test a hypothesis that the core biosynthetic machines could have a surplus that is not needed to maintain steady growth but is beneficial for adapting to a new condition. This project will experimentally test this hypothesis by employing perturbations of the abundance of core biosynthetic machines and quantitative measurements of the effect on the rates of growth and adaptation in single E. coli cells. This project will also establish a multiscale theoretical framework introducing redundancy to the core biosynthetic network to explain the experimental observations and make testable predictions. The expected outcomes of this project could reveal fundamental tradeoff strategies for growth and adaptation by controlling the abundance of cellular components.This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.