BIOPHYSICAL THEORY AND MODELING |
Sustained Oscillations in Extended Genetic Oscillatory Systems
Kwang-Il Goh 1, Byungnam Kahng 2 and Kwang-Hyun Cho 3*
1 Department of Physics, Korea University
2 School of Physics and Astronomy, Seoul National University
3 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology
* To whom correspondence should be addressed. E-mail: ckh{at}kaist.ac.kr.
Submitted on December 18, 2007
Revised on January 23, 2008
Accepted on 23 January 2008
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Abstract |
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Various dynamic cellular behaviors have been successfully modelled in terms of elementary circuitries showing particular characteristics such as negative feedback loops for sustained oscillations. Given, however, the increasing evidences indicating that cellular components do not function in isolation but form a complex interwoven network, it is still unclear to what extent the conclusions drawn from the elementary circuit analogy hold for systems that are highly interacting with surrounding environments. In this paper, we consider a specific example of genetic oscillator systems, the so-called repressilator, as a starting point towards a systematic investigation into the dynamic consequences of the extension through interlocking of elementary biological circuits. From in silico analyses with both continuous and Boolean dynamics approaches to the 4-node extension of the repressilator, we found that (i) the capability of sustained oscillation depends on the topology of extended systems, and (ii) the stability of oscillation under the extension also depends on the coupling topology. We then deduce two empirical rules favoring the sustained oscillations, termed the coherent coupling and the homogeneous regulation. These simple rules will help us prioritize candidate patterns of network wiring, guiding both the experimental investigations for further physiological verification and the synthetic designs for bioengineering.
Key Words:
Biological network, Feedback loop, Sustained oscillation