Quantitative Biology / Gene Expression in Development & Disease Seminar

Friday, 15 March 2013 at 11:30am

Room 1400 Biomedical and Physical Sciences Bldg.

Refreshments at 11:30

Speaker:  Oleg Igoshin, Department of Bioengineering, Rice University

Title:  Ultrasensitivity and Stochasticity in Bacterial Networks (System Dynamics of Bacterial Gene Regulatory Networks that Control Development)

The rate laws describing kinetics of biochemical reactions are fundamentally non-linear[1]. These non-linearities are responsible for many key dynamical properties of biochemical networks. Often these result in ultrasensitive switches in which small changes or fluctuations of network inputs can lead to a large change in network output. Such switches are important for making robust cell decisions but can be detrimental for networks functioning in homeostasis and desiring noise minimization. In this presentation I'll discuss biological examples illustrating each of these cases.

In the first story[2], with combination of mathematical modeling and bioinformatic data analysis, we show that noise minimization and avoidance of ultrasensitive switches explain operon organization of E. coli. We hypothesized that operons alter gene expression noise characteristics, resulting in selection for or against maintaining operons depending on network architecture. Mathematical models for six functional classes of network modules showed that three classes exhibited decreased noise and three exhibited increased noise with same-operon cotranscription of interacting proteins. Ultrasensitive play major role in noise amplification for most of the modules. Further, we employed bioinformatic analysis of E. coli chromosome to find overrepresentation of noise-minimizing operon organization compared with randomized controls. These results suggest a central role for gene expression noise in selecting for or against maintaining operons in bacterial chromosomes, thereby providing an example of how the architecture of post-translational networks affects bacterial evolution.

In the second story[3], with combination of mathematical modeling and single-cell microscopy, we show the existence and origins of ultrasensitivity in the network responsible for cell-fate decision in sporulating B. subtilis. We infer that under uncertain conditions cells initiate sporulation but postpone making the sporulation decision in order to average stochastic fluctuations and to achieve robust population response. These results illustrate how unique structure of the sporulation network allows fast and robust population level response despite cellular variability.


  1. Ray JCJ, Tabor JJ, Igoshin OA (2011) Non-transcriptional regulatory processes shape transcriptional network dynamics. Nature Reviews Microbiology 9: 817-828.
  2. Ray JCJ, Igoshin OA (2012) Interplay of Gene Expression Noise and Ultrasensitive Dynamics Affects Bacterial Operon Organization. PLoS Comput Biol 8: e1002672.
  3. Narula J, Devi SN, Fujita M, Igoshin OA (2012) Ultrasensitivity of the Bacillus subtilis sporulation decision. Proc Natl Acad Sci U S A 109: E3513-E3522.