Critical points, fitness, and evolution in natural and synthetic biological networks
Physiological responses in growing organisms display tradeoffs between cost and benefit. In microbial metabolism, organismal fitness (often characterized by population growth rate) depends on networks of well-balanced metabolic fluxes. In gene regulation and signaling networks, physical limits on information flow play a decisive role in evolution. In either type of network, small-scale molecular mechanisms can have a powerful effect on larger-scale emergent physiology, creating critical transitions that determine cellular phenotypes and thus fitness.
In my laboratory we are using complementary theoretical and experimental methods to understand the relationship between the properties of critical transitions in single cells and evolutionary fitness. We use mathematical and computational methods to predict cellular dynamics and guide the design of experiments with bacteria. In the laboratory we directly measure the relationship between network dynamics and fitness, using either natural networks (such as the well-studied lac operon in E. coli) or synthetic constructs designed to test specific predictions.
- Ray JCJ and Igoshin OA. (2012) Interplay of gene expression noise and ultrasensitive dynamics affects bacterial operon organization. PLoS Comput Biol 8(8): e1002672.
- Quan S, Ray JCJ, Kwota Z, Duong T, Balázsi G, Cooper TF, Monds RD. (2012) Adaptive evolution of the lactose utilization network in experimentally evolved populations of Escherichia coli. PLoS Genet 8(1): e1002444.
- Ray JCJ, Tabor J, and Igoshin OA. (2011) Non-transcriptional regulatory processes shape transcriptional network dynamics. Nat Rev Microbiol 9(11):817-828.
- Tiwari A, Ray JCJ, Narula J, Igoshin OA. (2011) Bistable responses in bacterial genetic networks: designs and dynamical consequences. Math Biosci 231(1):76-89.
- Ray JCJ and Igoshin OA. (2010) Adaptable functionality of transcriptional feedback in bacterial two-component systems. PLoS Comput Biol 6(2):e1000676.