Our research group perform a combination of theoretical and experimental studies at the interface of physics and biology, in an emerging area generally called quantitative biology, whose overall goal is to attain predictive understanding of living systems. Our focus is on bacteria, the simplest autonomous living systems, which nevertheless defy quantitative, predictive understanding at multiple stages, e.g., from molecular characteristics to cellular behaviors, and from cellular characteristics to population- and community- wide dynamics.
Since the birth of molecular biology, a basic scientific paradigm towards understanding biological function has been to elucidate the underlying molecular interactions. However, despite the many thousands of interactions revealed by rapid advances in ’omics technologies, many basic functions of living cells remain mysterious under this “bottom-up” approach. Over a decade ago, our lab developed a complementary “top-down” approach, starting with quantitative characterization of physiological behaviors of cells. Simple phenomenological models of bacterial growth control, built on empirical observations of growth-rate dependent proteome allocation, were formulated to make quantitatively accurate, parameter-free predictions relating protein expression and bacterial growth under a variety of environmental and genetic perturbations (Scott et al, Science 2010, Deris et al, Science 2013). Further quantitative methods of proteome analysis have been developed to establish simple rules of proteome allocation under a broad range of growth conditions (Hui et al, MSB 2015; Mori et al, MSB 2021). Extension of our approach has led to quantitative physiological understanding of a number of long standing bacterial phenomena including catabolite repression (You et al, Nature 2013), diauxic shift (Erickson et al, Nature 2017), and metabolic overflow (Basan et al, Nature 2015), as well as uncovering new phenomena, such as tradeoff between fast growth and rapid adaptation (Basan et al, Nature 2020) and hierarchical recovery of biosynthesis during adaptation of growth from rich to minimal media (Wu et al, Nature Microb. in press). Quantitative top-down approaches have also enabled elucidation of molecular strategies underlying global regulation, including cyclic AMP signaling (You et al, Nature 2013), ppGpp signaling (Wu et al, PNAS 2022), and transcription-translation coordination (Balakrishnan et al, Science, in press).
In the past several years, we have further extended our quantitative physiological approaches to study spatiotemporal dynamics of bacterial population and their evolution, in the context of biofilm composition (Warren et al, eLife 2019) and chemotaxis (Cremer et al, Nature 2019; Liu et al, Nature 2019). We have also expanded our studies beyond model organism (mostly E. coli) in ideal laboratory conditions, to e.g., gut microbes in colonic flow environment (Cremer et al, PNAS 2016; Cremer et al, PNAS 2017) and under acid stress (Taylor et al, in review). We are also investigating microbial interactions within communities (Amarnath et al, in review), taking examples from marine microbial communities. Current research are in the following areas: