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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Systems biology towards life in silico: Mathematics of the control of living cells
Journal of Mathematical Biology, Volume 58, No. 1-2, Year 2009
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Description
Systems Biology is the science that aims to understand how biological function absent from macromolecules in isolation, arises when they are components of their system. Dedicated to the memory of Reinhart Heinrich, this paper discusses the origin and evolution of the new part of systems biology that relates to metabolic and signal-transduction pathways and extends mathematical biology so as to address postgenomic experimental reality. Various approaches to modeling the dynamics generated by metabolic and signal-transduction pathways are compared. The silicon cell approach aims to describe the intracellular network of interest precisely, by numerically integrating the precise rate equations that characterize the ways macromolecules' interact with each other. The non-equilibrium thermodynamic or 'lin-log' approach approximates the enzyme rate equations in terms of linear functions of the logarithms of the concentrations. Biochemical Systems Analysis approximates in terms of power laws. Importantly all these approaches link system behavior to molecular interaction properties. The latter two do this less precisely but enable analytical solutions. By limiting the questions asked, to optimal flux patterns, or to control of fluxes and concentrations around the (patho)physiological state, Flux Balance Analysis and Metabolic/Hierarchical Control Analysis again enable analytical solutions. Both the silicon cell approach and Metabolic/Hierarchical Control Analysis are able to highlight where and how system function derives from molecular interactions. The latter approach has also discovered a set of fundamental principles underlying the control of biological systems. The new law that relates concentration control to control by time is illustrated for an important signal transduction pathway, i.e. nuclear hormone receptor signaling such as relevant to bone formation. It is envisaged that there ismuch more Mathematical Biology to be discovered in the area between molecules and Life. © Springer-Verlag 2008.
Authors & Co-Authors
Westerhoff, Hans Westerhoff V.
Unknown Affiliation
Kolodkin, Alexey
Unknown Affiliation
Conradie, Riaan
Unknown Affiliation
Wilkinson, Stephen J.
Unknown Affiliation
Bruggeman, Frank J.
Unknown Affiliation
Krab, Klaas
Unknown Affiliation
van Schuppen, Jan H.
Unknown Affiliation
Hardin, Hanna
Unknown Affiliation
Bakker, Barbara Marleen
Unknown Affiliation
Moné, Martijn J.
Unknown Affiliation
Rybakova, Katja N.
Unknown Affiliation
Eijken, Marco
Unknown Affiliation
Van Leeuwen, Johannes P.T.M.
Unknown Affiliation
Snoep, Jacky L.
Unknown Affiliation
Statistics
Citations: 90
Authors: 14
Affiliations: 6
Identifiers
Doi:
10.1007/s00285-008-0160-8
ISSN:
03036812
e-ISSN:
14321416
Research Areas
Cancer
Noncommunicable Diseases