Discrete Event Simulation of Biological Control Processes and its Application to Autonomous Decision-Making in Manufacturing Systems
ESPRC Funded Project

Previous Research Track Record

Professor David Stockton – De Montfort University (Principal Investigator)

Since 2001 Professor Stockton has been awarded 4 EPSRC projects totaling approximately £600,000 and 2 DTI awards totalling £670k. He is a former member of the EPSRC Peer Review College, member of the UK Manufacturing Professors Forum, committee member of the Consortium of Manufacturing Engineering Heads (COMEH) and a member of the editorial board of the Journal of Aircraft & Aerospace Technology. He frequently reviews for leading international journals including IJPR, IJCIM, Proc.of IMechE: Part B Engineering Manufacture and has been an external PhD examiner at Bath, Loughborough, Warwick and Cranfield universities. His latest research, related to this project, includes work on operations based problem solving, the introduction of lean practices and continuous problem solving processes, and implementing synchronous flow within high variety/low volume manufacturing environments. Previous related projects have included:

1. Self-Structuring Drum-Buffer-Rope Systems (2003-2006) - Industrial Collaborators: Taylor Hobson Ltd - This research funded by EPSRC combined Genetic Algorithms with simulation modelling to automatically identify manufacturing bottleneck processes, and develop optimum schedules and buffer sizes.
2. Measuring The Effects Of Variation On Flow Processing Lines (2000-2004) - Industrial Collaborators: Rolls-Royce PLC and Lear Corporation - This research looked at methods of both measuring levels of variability and of the effects of variation within mixed model flow processing systems.
3. Automatic Design And Optimisation Of Manufacturing Systems (2001-2004) - Industrial Collaborators: Advanced Engineering Systems & Ketlon UK of Unipart Industries, Foggini Key Europe, Bridgeport Machines Ltd, Visual Thinking International Ltd, ISIS Informatics Ltd, Preactor International Ltd, Cross-Hueller, Castillion Precision Engineering Ltd – This project involved the integration of simulation and optimization methods to design manufacturing systems and was rated Tending to Internationally Leading, by the EPSRC, ie IMI EPSRC SimFML - Responsive Design & Operation of Flexible Machining Lines (GR/N05871) and the RAIS - Responsive Design and Operation of Flexible Machining Lines (GR/S77127/01).
4. Intelligent Design Of Manufacturing Systems(1994-1996) - Industrial Collaborators: Bridgeport Machines Ltd, Bostic Ltd, Foggini Key Europe - This research, funded by EPSRC examined evolutionary optimisation techniques for making decisions that overcame many of the limitations of existing traditional operations planning techniques.

Professor Stockton’s relevant publications include:

• Stockton D.J., Quinn, L. & Khalil, R. A., 2004, “Uses of Genetic Algorithms in Operations Management Part I – Applications”, Proc. IMechE: Part B: J. of Engineering Manufacture, 218/B3, pp 315-27.
• Stockton D.J., Quinn, L. & Khalil, R. A., 2004, “Uses of Genetic Algorithms in Operations Management Part II - Results”, Proc. IMechE: Part B: J. of Engineering Manufacture, 218/B3, pp 329-43.
• Khalil, R.A., Stockton, D.J. and Fresco. J.A., “Predicting the Effect of Common Levels of Variability in Flow Processing Systems”, Accepted for publication in the Int. J. of Computer Integrated Manufacturing, 2007.
• Stockton D. J., Khalil, R. et al, 2006, “Designing multi-component flexible manpower lines”, Transactions of the Japanese Society of Automotive Engineers, Vol. 37, No. 1, pp 141-146.
• Ardon-Finch J.P., Stockton D. J., & Khalil, R., 2005, "Walk cycle design for flexible manpower lines using genetic algorithms", Int. J. of Comp Int. Manuf’ing, 18/1, pp 15-26.
• Ardon-Finch J.P., Stockton D. J., & Khalil, R., 2005, "Design of flexible manpower line walk cycles for a fixed number of operators", Int. J. of Prod. Res. 43/3, pp 583-96.

Dr Maria Schilstra – University Of Hertforshire

Dr Maria Schilstra (PhD 1986 Biochemistry/Biophysics, MSc 2000 Computer Science) holds an open-ended Senior Research Fellowship in BioComputation, and, since early 2006, leads the BioComputation Research Group, which is one of the two branches of the Biological & Neural Computation Group at the University of Hertfordshire (UH). The Group is located in the Science and Technology Research Institute (a dedicated multidisciplinary research facility at UH with a current grant portfolio of £8.1M), and has strong links with groups at the Systems Biology Institute in Seattle, Caltech, EMBL-EBI and the MRC-Biostatistics Unit (Cambridge, UK), MRC-NIMR (London), and, through SBML (see below) other Computational Systems Biology groups world-wide.

Dr Schilstra has an established reputation in Systems Biology, many years of experience in experimental biochemistry and biophysics, and computational modelling of enzyme systems and regulatory networks. She is a former member of the SBML Core Team, and now specializes in computational approaches, especially stochastic and hybrid stochastic-deterministic, to the study of biological systems in general. Ongoing projects in the BioComputation Group include:

1. Netbuilder - The NetBuilder project is currently supported by a £200k grant from the Wellcome Trust (to M. J. Schilstra and C. L. Nehaniv, Research Professor of Mathematical and Evolutionary Computer Science at UH) under its Functional Genomic Programme, and by QR funding to the School of Computer Science at UH. The project involves creating a suite of platform-independent open-source computational tools that can be used by relatively inexperienced (such as experimental biologists) as well as experienced modellers to study complex regulatory systems. Models are represented as timed Petri-nets, organized in a hierarchical layer structure, which are capable of capturing the topology as well as the dynamics of the networks in a thermodynamically justifiable way. NetBuilder provides a selection of algorithms (stochastic or deterministic, discrete or continuous) to simulate the responses of the modelled networks to external stimuli or changed conditions. The tools provided can be applied to a wide range of biochemical networks, but have been designed for - and are, therefore are particularly suited to - the modelling and simulation of combinatorial effects of multiple effectors, such as the ones that form the basis of genetic regulatory networks.
2. SBML - The Systems Biology Markup Language (SBML) is the de-facto standard format for storage and exchange of biochemical network models. The group is heavily involved in the specification of the language, and in the work on SBML-related tools, specifically the MATLAB SBMLtoolbox, and the API libSBML
3. Evolvability Studies On Grns – Studies into the evolvability of artificial ‘genetic regulator networks’ (GRNs) are undertaken in collaboration with Prof. C. L. Nehaniv in order to abstract useful principles from biological GRNs and their evolution to aid novel computation and automated complex systems engineering.
4. Algebraic Coordinization Of Complex Systems> – Under the direction of Prof. C. L. Nehaniv, computational tools are being developed that implement holonomy decomposition of finite state automata on the basis of Krohn-Rhodes theory. The aim is to assess the applicability of the theory and tools to the hierarchical decomposition of models of biological regulatory networks, and to develop a plug-in for the NetBuilder suite.

Dr Schilstra’s recent relevant publications include:

• Schilstra, MJ, Martin, SR, and Keating, SM: Methods for simulating the dynamics of complex biological processes, Biophysical tools for the biologist, Vol. 1, eds. JJ Correia and WH Dietrich, Methods in Molecular Biology, eds L Wilson and PT Matsudaira, Elsevier Inc., San Diego (to appear early 2007)
• Le Novere, N, Bornstein, B, Broicher, A, Courtot, M, Donizelli, M, Dharuri, H, Li, L, Sauro, H, Schilstra, M, Shapiro, B, Snoep, JL, and Hucka, M (2006) BioModels Database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems. Nucl. Acids Res. 34, D689-691.
• Schilstra, MJ and Martin, SR (2006) An elastically tethered viscous load imposes a regular gait on the motion of myosin-V. Simulation of the effect of transient force relaxation on a stochastic process. J. Royal. Soc. Interface 3, 153-165.
• Schilstra, MJ, Li, L, Matthews, J, Finney, A, Hucka, M, and Le Novere, N (2006) CellML2SBML: conversion of CellML into SBML. Bioinformatics 22, 1018-1020.
• Hucka, M, Finney, A, Bornstein, B, Keating, SM, Shapiro, BE, Matthews, J, Kovitz, B, Schilstra, MJ, Funahashi, A, Doyle, JC, and Kitano, H (2004) Evolving a Lingua Franca and Associated Software Infrastructure for Computational Systems Biology: The Systems Biology Markup Language (SBML) Project. Systems Biology 1, 41-53.
• Davidson, EH, Rast, JP, Oliveri, P, Ransick, A, Calestani, C, Yuh, C-H, Minokawa, T, Amore, G, Hinman, V, Arenas-Mena, C, Otim, O, Brown, CT, Livi, CB, Lee, PY, Revilla, R, Rust, AG, Pan, Zj, Schilstra, MJ, Clarke, PJC, Arnone, MI, Rowen, L, Cameron, RA, McClay, DR, Hood, L, and Bolouri, H (2002) A Genomic Regulatory Network for Development. Science 295, 1669-1678.