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Network Structure and Robustness of Intracellular Oscillators
KTH, School of Electrical Engineering (EES), Automatic Control.
KTH, School of Electrical Engineering (EES), Automatic Control.
2008 (English)In: 17th World Congress, International Federation of Automatic Control, IFAC, 2008Conference paper (Refereed)
Abstract [en]

Sustained oscillations play a key role in many intracellular functions, such as circadian time keeping, cell cycle control and calcium signalling. The oscillations are in all cases driven by feedback interactions taking place in biochemical reaction networks. While a single feedback loop in principle is sufficient to generate such oscillations, experimental evidence reveal that more complex network structures, involving multiple feedback loops, underly intracellular oscillations. One hypothesis frequently set forth is that a multi-loop structure is motivated by the need for robustness to internal and external perturbations. We here consider robustness analysis of several recently published models of circadian clocks to determine the role of the underlying network structure in providing robust stability of the oscillators. The robustness analysis is based on adding dynamic perturbations to the network interactions, similar to that used in robust control theory. To elucidate the role of various interactions in providing robust oscillations, we consider blocking specific interactions. Biologically, this contrasts the often considered gene knockouts and implies that genes are persistently expressed. We find that different models have highly different active structures and also differ significantly in their robustness. While some models essentially rely on a single loop in generating robust oscillations, other models have more intricate structures in which some loops provide oscillations and other serve to increase the robustness. Other models again have redundant loops that provide failure tolerance in the face of large perturbations, such as gene knockouts.

Place, publisher, year, edition, pages
, IFAC Proceedings Volumes, ISSN 14746670 ; 17
Keyword [en]
Design and control, Estimation and control in systems biology, Process modeling and identification
National Category
Control Engineering Bioinformatics and Systems Biology
URN: urn:nbn:se:kth:diva-88896DOI: 10.3182/20080706-5-KR-1001.3617OAI: diva2:502546
17th World Congress, International Federation of Automatic Control, IFAC. Seoul. 6 July 2008 - 11 July 2008
QC 20120216Available from: 2012-02-14 Created: 2012-02-14 Last updated: 2012-02-16Bibliographically approved

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Trané, CamillaJacobsen, Elling W.
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