Systems Biology at S3 - Automatic Control

The process control group has recently started up a new research effort directed towards modelling and analysis of intracellular processes. The primary aim of this research is to unravel the functional interactions between the various components of the cell; DNA, RNA, proteins and metabolites. This is important since most of the functions in a cell are a result of feedback interactions between a large number of components, and typically involve a substantial number of genes and gene products. Thus, linking the physiology of living cells (phenotype) to the information encoded in the genome (genotype), will require an understanding of how interactions create behavior in intra- and intercellular networks.

We consider genetic, metabolic as well as signal transduction networks. Our contributions in this area will come from applying systems theory, in general, and model based tools developed for large scale process systems, in particular, to modelling and analysis of cellular networks.

Initially, we have considered quantitative modelling of intracellular networks from time-series measurements, decomposition of cell networks into functional subnetworks and identification of critical feedback interactions underlying specific cell functions.

The research in Systems Biology is funded by the Swedish Research Council (Vetenskapsrådet).

Some recent publications within systems biology are

S. Waldherr, F. Allgöwer and E.W. Jacobsen, ''Kinetic perturbations as robustness
analysis tool for biochemical reaction networks'', submitted to 2009 IEEE CDC

T.N. Nordling and E.W. Jacobsen, ''Interampatteness -- A Generic Property of Biochemical Networks'', IET Systems Biology, to appear (2009)

E.W. Jacobsen and C. Trane, ''Structural Robustness of Biochemical Networks'', In Control Theoretic Approaches in Systems Biology, Eds. B. Ingalls and P. Iglesias, MIT Press, to appear 2009

E.W. Jacobsen and C. Trane, ''Using Dynamic Perturbations to Identify Fragilities in Biochemical Reaction Networks'', International Journal of Robust and Nonlinear Control, invited paper submitted (2009)

E.W. Jacobsen and G. Cedersund, "Structural Robustness of Biochemical Network Models - with Application to the Oscillatory Metabolism of Activated Neutrophils", IET Systems Biology, No.1, Vol. 2, 2008

C. Trane and E.W. Jacobsen, ''Network Structure and Robustness of Intracellular Oscillators'', IFAC World Congress, Seoul, July 2008

T. Nordling and E.W. Jacobsen, ''Ill-Conditioning - A Property of Bio-Networks'', 2nd q-bio Conference on Cellular Information Processing, Santa Fe, August 2008

M. Hellgren, T.N. Nordling, E.W. Jacobsen and J-O. Höög, "Multi-level modelling of the parallel metabolism of ethanol and retinol, with implications for foetal alcohol syndrome", International Conference on Systems Biology, Gothenburg, August 2008

T.N. Nordling and E.W. Jacobsen, ''Inference of interampatte gene regulatory networks - with application to apoptosis signalling'', International Conference on Systems Biology, Gothenburg, August 2008

Camilla Trané and Elling W. Jacobsen, "On Robustness as the Rationale Behind Multiple Feedback Loops in the Circadian Clock", Proceedings of Foundations of Systems Biology in Engineering (FOSBE), 2007

Torbjörn E. M. Nordling, Noriko Hiroi, Akira Funahashi, "Dynamic modes in biological systems: Why should a biologist care?", The 8th International Conference on Systems Biology (ICSB-2007), Long Beach (U.S.A.), 2007

Torbjörn E. M. Nordling, Elling W. Jacobsen, "Experiment Design for Proper Excitation of Gene Regulatory Networks", Proceedings of Foundations of Systems Biology in Engineering (FOSBE), 2007

Torbjörn E. M. Nordling, Noriko Hiroi, Akira Funahashi, Hiroaki Kitano, " Deduction of intracellular sub-systems from a topological description of the network", Molecular BioSystems, 3, 523-529, 2007

Torbjörn E. M. Nordling, Elling W. Jacobsen, " Experiment design for optimal excitation of gene regulatory networks", The 7th International Conference on Systems Biology (ICSB-2006), Yokohama (Japan), 2006

Camilla Trané and Elling W. Jacobsen, "Unraveling Feedback Structures in Gene Regulatory Networks with Application to the Mammalian Circadian Clock", The 7th International Conference on Systems Biology (ICSB-2006), Yokohama (Japan), 2006

Camilla Trané and Elling W. Jacobsen, "Multiple Feedback Loops Provide Robust Osciallations in the Mammalian Circadian Clock", International Workshop on Systems Biology, Maynooth (Ireland), 2006

H. Schmidt and E.W. Jacobsen, "Linear Systems Approach to Analysis of Complex Dynamic Behaviours in Biochemical Networks", Systems Biology, No. 1., Vol. 1 (Inaugural Issue), June 2004

H. Schmidt and E.W. Jacobsen, "Identifying Feedback Mechanisms Behind Complex Cell Behavior", IEEE Control Systems Magazine, No. 4, Vol. 24, 91-102 (Special Issue on Biochemical Networks and Cell Regulation), August 2004

H. Schmidt, K.H. Cho and E.W. Jacobsen, "Identification of Small Scale Biochemical Networks based on General Type System Perturbations'', FEBS Journal, No. 9, Vol. 272, 2141-2151, May 2005

E.W. Jacobsen and G. Cedersund, "On Parametric Sensitivity and Structural Robustness of Cellular Functions -- the Oscillatory Metabolism of Activated Neutrophils", Invited paper for CDC-ECC'05, Seville, Spain, December 2005

H. Schmidt and E.W. Jacobsen, "A Linear Systems Approach to the Analysis of Complex Behaviors within Biochemical Reaction Networks - Application to the Cell Cycle", 4th International Conference on Systems Biology, St Louis, November 2003

H. Schmidt, K.-H. Cho and E.W. Jacobsen, ``Identification of Feedback Loops in Metabolic Pathways'', 5th International Conference on Systems Biology, Heidelberg, Germany, October, 2004

H. Schmidt and E.W. Jacobsen, ``On the Decomposition of Dynamic Metabolic Networks'', 5th International Conference on Systems Biology, Heidelberg, Germany, October 2004

H.Schmidt and E.Jacobsen, "Analysis of Bifurcation Behavior in Biochemical Reaction Networks with Application to the Cell Cycle", AIChE Annual Meeting, San Francisco, November 2003.

Contact: Elling W. Jacobsen