Exploiting Biological Noise for Reliable Cell-Fate Decision and Novel Cellular Phenotype Generation
Kyung Hyuk Kim
Acting Assistant Professor
March 12, 2015
Foege N130A, Wallace H. Coulter Seminar Room
Cellular processes are stochastic due to the underlying processes being random in nature. In addition many cellular processes show nonlinear behavior. It is of interest to understand the interplay between stochasticity and nonlinearity and whether the interplay is exploited by natural systems. Moreover it is important to know whether we can exploit stochasticity and nonlinearity in engineered systems. This talk will include both theoretical and experimental studies on biological noise. First, mathematical and computational frameworks for modeling and shaping the noise will be briefly discussed. The frameworks enable us to identify which system parameters need to be perturbed and by how much. Second, an intuitive but fully quantitative approach to understanding noise-induced phenotypes will be presented. This approach successfully describes how the interplay between stochasticity and nonlinearity induces various cellular phenotypes such as noise-induced bistability, noise-enhanced concentration detection, and noise-induced linear amplification. Lastly, my recent experimental results on noise control in E. coli gene expression will be presented. I will show that cell-to-cell variability of intracellular transcription factor concentrations can be controlled and varied up to ten fold while mean concentrations remain fixed. This control was also applied to observe whether Hill coefficients in genetic regulation are affected by the variability. Lastly, I will discuss about how to control cell-fate decision in HIV infection and to enhance efficiency in stem cell differentiation via the proposed noise-control method. In summary, this study will help understand how biological noise is exploited by natural biological systems and how engineers can take into account stochasticity and nonlinearity in a systematic and predictable way.
Dr. Kyung Hyuk Kim is currently an Acting Assistant Professor in the Department of Bioengineering at the University of Washington. He received his Ph.D. degree in Physics from the University of Washington in December 2006. From 2007 to 2012, he worked as a Senior Fellow in the Sauro lab at the UW Bioengineering. His research interests include (1) mathematical and statistical modeling of biological systems including metabolic, gene regulatory, and protein signaling networks and (2) experimental characterization of synthetically engineered cells. He has authored or co-authored 21 journal papers and 3 book chapters and has a track record of writing two successful grant proposals (NSF Molecular and Cellular Biosciences, and NSF Theoretical Biology).