Systems Biology in Kent is an attempt to represent Biology as a System and to apply to it the full power of various system-specific techniques developed in physical, engineering and philosophical sciences. At Kent, we develop a number of Engineering-based Systems Biology approaches that enhance our understanding of cellular signalling in single cell systems as well as in multicellular organisms. We analyse new experimental data interpretation avenues that lead to novel diagnostic and predictive techniques.
Professor Sarah Spurgeon and Dr Naji Valeyev have expertise in ‘Translational Systems Biology: the development of systems biology modelling strategies that meet the needs of translational medicine’ and ‘Development and application of modern Systems Biology techniques to elucidate the underlying molecular mechanisms of cellular signalling’.
Dr Yong Yan, Dr Gary Lu and Professor Sarah Spurgeon hold expertise in ‘Instrumentation, measurement, and condition monitoring’.
Professor Sarah Spurgeon, Dr Naji Valeyev and Dr Yong Yan also have expertise in ‘Applications of advanced control and parameter estimation approaches to molecular systems’.
Areas of interest
Measurement and monitoring
- Measurement of certain key parameters
- Monitoring of system states and conditions
Control and modelling
- Estimation of parameters and nonlinear effects
- Model synthesis and analysis (whereby the tools can report how close a model represents real data).
- The synergy between the natural regulation processes in biological systems and the engineering control design paradigms can be harnessed to enhance the performance of both biological and engineering systems.
Translational systems biology
Systems modelling offers unique advantages to biomedical research. It allows unambiguous integration of multiple separately acquired pieces of experimental data into a comprehensive model that magnifies the power of experimental interpretation beyond the level of intuitive conclusions. For example, it becomes possible to predict what available antibodies or compounds are likely to eliminate pathologic inflammation. In a number of cases, systems modelling offers indirect target identification approaches providing the opportunity for novel interventions by using already available therapeutic agents. Systems modelling permits the study of the immune system as a system, where cell populations are interconnected and combinations of single nucleotide polymorphisms (SNP) or differentially expressed proteins can switch between normal and pathologic phenotypes. Therefore, it becomes possible to guide which and to what extent indirect non-SNP associated interventions are likely to have an impact on the overall immune system in order to reduce pathology.
Cross-disciplinary research and projects
Sliding Mode Observer-based control for a Continuous Fermentation Process
Funded By: Ministry of Higher Education (MOHE), Malaysia
Period: 01/10/2007 – 30/9/2010
In a fermentation system, the biomass balance and the substrate mass balance are coupled by a nonlinear growth rate condition. In order to control the resulting nonlinear process, many researchers assume that both substrate and biomass concentration are measurable. In practice, only online measurement of substrate concentration is possible. This project considers the development of a soft sensor, or observer, which can estimate a relaxed state, the substrate consumption rate. This quantity is a combination of the substrate concentration, biomass concentration, specific growth rate and yield production coefficient. This parameterisation is used to simplify the nonlinear differential equations that represent the fermentation process and yields a convenient controller implementation. The method is robust to parameter and model uncertainty as well as disturbances.
Lister, S.J., Spurgeon, S.K., and Scott, J.J.A., Second-Order Sliding-Mode Control As an Alternative to Static and Dynamic Optimisation in Human Gait Simulation, Proceedings of the European Control Conference 2007, July 2-5, 2007, Kos, Greece.
Lai, N.O., Edwards, C., and Spurgeon, S.K., On Output Tracking Using Dynamic Output Feedback Discrete-Time Sliding Mode Controllers, IEEE Transactions on Automatic Control, Vol. 52, No. 9, September 2007.
Floquet, T., Edwards, C., and Spurgeon, S.K., On sliding mode observers for systems with unknown inputs, International Journal of Adaptive Control and Signal Processing, Volume 21, Issue 8-9 , 638 – 656, 2007.
Gilabert G, Lu G, Yan Y, ‘Three-dimensional tomographic reconstruction of the luminosity distribution of a combustion flame’, IEEE Transactions on Instrumentation and Measurement, Vol.56, No.4, pp.1300-1306, 2007.
Valeyev, N. V., Bates, D. G., Heslop-Harrison, P., Postlethwaite, I. and Kotov, N., “Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach”, BMC Systems Biology, Vol. 2(48), 2008.
Valeyev, N.V., Heslop-Harrison, P., Postlethwaite, I., Kotov, N. and Bates, D. G., “Multiple calcium binding sites make calmodulin multifunctional”, Molecular Biosystems, Volume 4, Issue 1, pp. 66 – 73, 2008.
Spurgeon, S.K., Sliding mode observers – A Survey, International Journal of Systems Science, invited survey paper, Volume 39, Issue 8, August 2008, pp. 751 – 764.
Carter R M, Yan Y, ‘The effect of illumination wavelength on the measurement of size distribution of very small particles using a novel imaging based system’, Particle & Particle Systems Characterization, Vol.25, No.4, pp.298-305 2008.
N. V. Valeyev, P. Heslop-Harrison, I. Postlethwaite, N. Kotov and D. G. Bates, “Crosstalk between G-protein and Ca2+ pathways switches intracellular cAMP levels”, Molecular Biosystems, 5, 43 – 51, 2009,
Seuret, A., Edwards, C., Spurgeon, S.K., and Fridman, E., Static output feedback sliding mode control design via an artificial stabilizing delay, IEEE Transactions Automatic Control, Volume 45, Issue 2, February 2009, pp. 256-265.
Han, X, Fridman, E., Spurgeon, S.K., and Edwards, C., On the Design of Sliding Mode Static Output Feedback Controllers for Systems with State Delay, IEEE Transactions on Industrial Electronics, Volume 56, Issue 9, Sept. 2009, pp. 3656 – 3664.
Andrade da Silva, J.M., Edwards, C., and Spurgeon, S.K., Sliding Mode Output Feedback Control Based on LMIs for Plants with Mismatched Uncertainties, IEEE Transactions on Industrial Electronics, Volume 56, Issue 9, Sept. 2009, pp. 3675 – 3683.
Krabicka J, Yan Y, ‘Finite-element modeling of electrostatic sensors for the flow measurement of particles in pneumatic pipelines’, IEEE Transactions on Instrumentation and Measurement, Vol.58, No.8, pp.2730-2736, 2009.
Kim, J.S., Valeyev, N.V., Postlethwaite, I, Heslop-Harrison P, Cho, K-H, Bates, D.G., Extension and Analysis of a Biochemical Network Model using Robust Control Theory, to appear in a Special Issue of the International Journal of Robust and Nonlinear Control on “Robustness in Systems Biology”, 2009
Valeyev, N.V., Kim, J.S., Heslop-Harrison, P, Postlethwaite, I, Kotov, N.V., Bates, D.G., Computational modelling suggests dynamic interactions between Ca2+, IP3 and G protein-coupled modules are key to robust Dictyostelium aggregation, Mol Biosyst. 2009 Jun;5(6):612-28
Valeyev, N.V., Downing, A.K., Sondek, J, Deane, C., Electrostatic and Functional Analysis of the Seven-Bladed WD beta-Propellers, Evol Bioinform Online. 2008;4:203-16
Kotov, N.V., Baker, R.E., Platov, K, Dawidov, D, Valeyev, N.V., Skorinkin, A.I., Maini, P.K., A study of the temperature dependence of bienzyme systems and enzymatic chains, Computational and Mathematical Methods in Medicine. 2007;2 (8):93-122
Valeyev, N.V., Downing, A.K., Skorinkin, A.I., Campbell, I.D., Kotov, N.V., A calcium-dependent mechanism regulates cell migration: a mathematical model, In Silico Biol. 2006;6(6):545-72
Hambleton S, Valeyev NV, Muranyi A, Knott V, Werner JM, McMichael A, Handford PA, Downing AK. “Structural and functional properties of the human Notch-1 ligand binding region” // Structure Journal. 12(12):2173-83, 2004
O’Leary JM, Hamilton JM, Deane CM, Valeyev NV, Sandell LJ, Downing AK. “Solution structure and dynamics of a prototypical chordin-like cysteine-rich repeat (VWC module) from collagen IIA” // J Biol Chem. 17;279(51):53857-66. 2004
Valeyev, N.V., Bates, D.G., Umezawa, Y, Gizatullina, A.N., Kotov, N.V., Chapter “Systems biology of cell behaviour” in the “Systems Biology in Drug Discovery and Development: Methods and Protocols” book. The volume is part of the “Methods in Molecular Biology” series published by Humana Press/Springer. 2009
Memberships of learned societies
Professor Sarah Spurgeon was elected to Fellowship of the Royal Academy of Engineering in 2008 with citation ‘Eminent for fundamental contributions to the development of nonlinear control and estimation methods, from theoretical developments through to trials and subsequent industrial support of technological exploitation’.