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

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

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, 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.