Recent News

2011-11
Seminar at the Institute of Systems Biology on Stochasticity and modularity in synthetic gene regulatory systems

2011-2
Genome Sciences/CMB Program Combi Seminar at the University of Washington on Fan-out Considerations and Noise Control of Synthetic Gene Circuits

2010-6

IWBDA: International Workshop on Bio-Design Automation at DAC. Oral presentation on Fan-out Considerations in Gene Regulatory Networks


2010-1

MBI Workshop 3: Synthetic Biology. Oral presentation on Control of Noise and Measures of Modularity in Synthetic Networks


2009-9

2nd Workshop on Stochasticity in Biochemical Reaction Networks. Banff, BC. Oral presentation on Sensitivity Analysis and Module Interface Conditions on Stochastic Gene Circuits


2008-10

2008 BMES Annual Fall Meeting. Oral presentation on Systems and Synthetic Biology: A Match Made in Heaven


2008-8

NSF (Advancing Theory in Biology) has decided to fund my research on stochastic extension of metabolic control analysis (PI:Herbert).


2008-8

ICSB poster presentation on Noise Propagation and Sensitivity for Stochastic Reaction Networks

Kyung Hyuk Kim

Post-doctoral Senior Fellow (Sauro Lab)

Department of Bioengineering
University of Washington at Seattle


Kids game "Spaceship Control" 
I made this C++ program for my son by using the Allegro library.
Here is its screenshotDownload

My research specialty is in computational and mathematical analysis of stochastic and deterministic biological models, specializing in the field of systems and synthetic biology.  

In recent years, gene regulatory networks have been synthetically designed and implemented for both basic research and specific application. Unlike other engineered systems such as electrical circuits or mechanical devices, cellular networks are inherently noisy due to the molecular nature of biochemical reaction events. This inherent stochasticity makes it difficult to characterize the functions of engineered cellular networks. In addition, context dependency and undesirable cross-talk between synthetic and natural systems make the characterization even more difficult. The noise can however be useful and exploited in systems ranging from cellular differentiation and viral fate decision, to system input-output responses.

During my doctoral studies, I conducted mathematical and computational (Monte-Carlo simulations) analyses on non-equilibrium stochastic processes under the direction of both Prof. den Nijs (Physics, University of Washington) and Prof. Qian (Applied Mathematics, University of Washington).

In my post-doctoral research, my main effort has been investigating stochastic biological networks with regard to modularity and stochasticity, by using my inter-disciplinary background knowledge and skills developed in physics and applied mathematics. I have been taking a leading role in supporting computational and mathematical research conducted by the group of Prof. Herbert Sauro (Bioengineering, University of Washington), in particular, focusing on synthetic network design and analysis. All my post-doctoral work was supported by an NSF grant in Theoretical Biology (awarded $660K), for which I wrote the main research plan. 



Research Topics                    


Gene regulatory networks:
  • Modularity
    • Applied the engineering concept of fan-out to gene regulatory networks for quantifying the degree of modularity (J. Biol. Eng).
    • Proposed an experimental method for measuring fan-out and retroactivity based on gene expression noise (Biophys. J).
    • Gene circuit analysis by mapping between gene regulatory networks and analog electrical circuits (future work, J. Biol. Eng).

  • Stochasticity
    • "Stochastic Control Analysis" (SCA): Developed a sensitivity analysis method for adjusting phenotypes by noise control (PLoS Computational Biology, Mathematical Biosciences).
    • Analyzed noise propagation and its effect on system sensitivities in reaction networks (submitted work).
    • Application of SCA to real biological systems such as stochastic switching in the HIV-1 long terminal repeat (LTR) promoter activity (future work).

  • Inter-cellular interactions and cellular communities
    • Provided a mathematical modeling and analysis of co-operative synthetic yeast strains in collaboration with Prof. Shou at the Fred Hutchinson Cancer Research Center (work in progress; reference). 

  • Evolution stability in synthetic genetic circuits
    • Designing fitness landscapes for gene regulatory networks (future work).

  • Characterizing and engineering cellular networks using stochastic measurements
    • Experimental verification of fan-out and retroactivity; Noise control for desired system functions such as circuit response and signal-to-noise ratios (future work).

Metabolic networks:
  • Extended the metabolic control analysis (MCA) to the stochastic regime (PLoS Computational BiologyMathematical Biosciences).

  • Visualization of signal propagation in biological networks (work in progress).

  • Metabolic flux optimization under the constraint of the total enzyme mass (work in progress).

Non-equilibrium statistical physics (graduate study):
  • Extended the Jarzynski equality and the fluctuation theorems for feed-back control systems (Physical Review E, Physical Review Letters)

  • One-dimension stochastic flow (two-species asymmetric exclusion process) and its universal scaling behaviors (critical phenomena) and phase transition (Phys. Rev. E)


Publications                          

K. H. Kim, H. Qian, and H. M. Sauro. Increasing the Sensitivity of Reaction Systems by Exploiting Stochastic Fluctuations. (Submitted)  

W. B. Copeland, D. Chandran, B. A. Bartley, M. Galdzicki, K. H. Kim, C. Maranas, S. C. Sleight, and H. M. Sauro. Computational Tools for Metabolic Engineering. (Submitted to Metabolic Engineering). 





K. H. Kim and H. Qian. Fluctuation Theorems of a Molecular Refrigerator. Phys. Rev. E 75, 022102 (2007)


Book Chapters

K.H. Kim, D. Chandran, and H.M. Sauro. Toward Modularity in Synthetic Biology: Design Patterns and Fan-out. In Heinz Koeppl, et al, Design and Analysis of Bio-molecular Circuits. Springer-Verlag. pp117-138 (2011)

Ph.D. Thesis 

Stochastic Driven Systems Far From Equilibrium (Advisors: Prof. Marcel den Nijs and Hong Qian)


Kyung Hyuk Kim

Department of Bioengineering
University of Washington
William H. Foege Building [UW map]
Box 355061
1705 NE Pacific St.
Seattle, WA 98195-5061