定量生物学中心学术报告
题目: Ultrasensitivity and stochasticity in bacterial networks.
报告人:Oleg Igoshin, Ph.D.
Associate Professor, Department of Bioengineering, Rice University
时间:2013-8-6(周二),14:00-15:00 PM
地点:北京大学老化学楼东配楼102会议室
主持人:定量生物学中心,汤超教授
Nonlinearities of rate laws describing biochemical reaction kinetics can often results in ultrasensitive switches in which small changes or fluctuations of parameters 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, 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 6 functional classes of network modules showed that three classes exhibited decreased noise and 3 exhibited increased noise with same-operon cotranscription of interacting proteins. 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, 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.
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