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We discuss the modern approaches of complexity and self-organization to understanding dynamical systems and how these concepts can inform current interest in systems biology. From the perspective of a physical scientist, it is especially interesting to examine how the differing weights given to philosophies of science in the physical and biological sciences impact the application of the study of complexity. We briefly describe how the dynamics of the heart and circadian rhythms, canonical examples of systems biology, are modelled by sets of nonlinear coupled differential equations, which have to be solved numerically. A major difficulty with this approach is that all the parameters within these equations are not usually known. Coupled models that include biomolecular detail could help solve this problem. Coupling models across large ranges of length- and time-scales is central to describing complex systems and therefore to biology. Such coupling may be performed in at least two different ways, which we refer to as hierarchical and hybrid multiscale modelling. While limited progress has been made in the former case, the latter is only beginning to be addressed systematically. These modelling methods are expected to bring numerous benefits to biology, for example, the properties of a system could be studied over a wider range of length- and time-scales, a key aim of systems biology. Multiscale models couple behaviour at the molecular biological level to that at the cellular level, thereby providing a route for calculating many unknown parameters as well as investigating the effects at, for example, the cellular level, of small changes at the biomolecular level, such as a genetic mutation or the presence of a drug. The modelling and simulation of biomolecular systems is itself very computationally intensive; we describe a recently developed hybrid continuum-molecular model, HybridMD, and its associated molecular insertion algorithm, which point the way towards the integration of molecular and more coarse-grained representations of matter. The scope of such integrative approaches to complex systems research is circumscribed by the computational resources available. Computational grids should provide a step jump in the scale of these resources; we describe the tools that RealityGrid, a major UK e-Science project, has developed together with our experience of deploying complex models on nascent grids. We also discuss the prospects for mathematical approaches to reducing the dimensionality of complex networks in the search for universal systems-level properties, illustrating our approach with a description of the origin of life according to the RNA world view.

Original publication




Journal article


J R Soc Interface

Publication Date





267 - 280


Animals, Biological Science Disciplines, Cell Physiological Phenomena, Circadian Rhythm, Computer Simulation, Heart, Humans, Models, Biological, Molecular Biology, Physics