Back to HomeKroto Research InstituteIntegrative Biology - the Epitheliome Project

Rod Smallwood, Jenny Southgate, Sheila Mac Neil, Mike Holcombe, Rod Hose, Richard Clayton, Rob Gaizauskas

Departments of Computer Science, Engineering Materials, and Medical Physics, University of Sheffield
Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York

If you cannot - in the long run - tell everyone what you have been doing, your doing has been worthless
(attributed to Erwin Schrödinger)

I believe very strongly that the fundamental unit, the correct level of abstraction, is the cell and not the genome
(Sydney Brenner, quoted in Denis Noble, The Music of Life)


The Epitheliome Project started in October 2001 when we began to use software agents as computational models of biological cells. The initial work (by Dawn Walker) was funded as part of an EPSRC Platform Grant (Rod Smallwood, Jenny Southgate, Freddie Hamdy and Mark Meuth). In 2005 we received substantial funding from EPSRC to continue the project (Rod Smallwood, Mike Holcombe, Jenny Southgate, Sheila Mac Neil, Richard Clayton, Rod Hose, Peter Hunter, and Rob Gaizauskas). A number of associated projects on cell signalling, re-stenosis in coronary arteries, and the microbial response to oxygen have been funded by BBSRC and EU FP7, and follow-on proposals have been submitted.

This web site provides background material on the Epitheliome Project, including a couple of unpublished papers which show how my ideas about modelling cellular interaction developed between 2003 and the end of 2009; a list of published papers; the names of everyone who has worked on the Project; and details of the software framework (FLAME) which we developed for the modelling.

Setting the scene

A cell-centred approach to modelling the behaviour of epithelial tissues has allowed us to explore the development of properly structured and functional tissue, and to look at the response of the tissue to insult such as wound healing. The behaviour of the individual cell in its mechanical and biochemical environment is central to these issues, and it seems self-evident that an exploration of cellular behaviour has to start from a model of the individual cell and its interaction with the environment. Physiome models in general do not encompass development - they are a snapshot of the behaviour of the system at a particular point in its development, and are unable to provide insight into either the processes that lead to the current state or future changes (the prognosis). My contention is that our modelling of cellular behaviour can provide this developmental perspective, and the tools we have developed allow our cellular models to be embedded in continuum models of tissue behaviour. The missing link is that between transcriptomics and cellular behaviour, and we have been developing this link.

Whilst the outputs from the Epitheliome Project have been fully described in the listed publications, the more general issues of how my thinking developed, and where we should be going in future, have only been explored in presentations. This background is provided by two papers, both of which were invited papers following conferences, which were not published (perhaps because they did deal with less concrete issues!). The first of these (Modelling emergent order: from individual cell to tissue) was written in 2003, shortly after the first paper (Walker et al 2004) on the epithelial model was submitted for publication. The second (Multiscale, multi-paradigm modelling of tissues: embedding development in tissue behaviour) was written late in 2009 following the IUPS meeting in Kyoto and presents my views on how development could be incorporated in physiological models.

Publications and Presentations

We have published a long list of papers in both technical and biological journals.


Eighteen people have worked on the Epitheliome Project since its inception in 2003.

FLAME (Flexible Large-scale Agent Modelling Environment)

FLAME has been developed to allow a wide range of agent and non-agent models to be brought together within one simulation environment.

FLAME provides specifications in the form of a formal framework which can be used by developers to create models, and software tools, that are compatible with one another. New models, adhering to the specifications, may be easily incorporated into existing, or new, simulations with minimum effort. Parallelisation methods and testing techniques, allow the development of large multiprocessor simulations with feedback provided on the functionality of written code.

Related Projects

Projects using models or software developed as part of the Epitheliome Project. For each project, only Epitheliome Project members are listed.

Coast (Complex Automata Simulation Technique) and Muscle (Multiscale Coupling Library and Environment). EU FP6 (Rod Hose, Dawn Walker, Rod Smallwood)

SUMO Systems Understanding of Microbial Oxygen Responses. Sysmo (Mike Holcombe)

The Virtual Tendon - A Multi-Scale Computational Model Of Dynamical Tissue Remodelling. Arthritis Research Campaign (Dawn Walker, Rod Hose)

Automated discovery of emergent misbehaviour. EPSRC (Phil McMinn)

A combined in vitro and in virtuo multiscale approach to understanding calcium signalling as a signature and integrator of cellular response. Wellcome Trust (Dawn Walker, Jenny Southgate)

Engineering Virus-like Nanoparticles for Targeting the Central Nervous System. EPSRC (Dawn Walker, Rod Smallwood)

Links to external sites

Read about the Virtual Physiological Human and the Epitheliome Project on Biomed Town

The Bioengineering Institute at the University of Auckland

The IUPS Physiome Project

The EuroPhysiome

The Renal Physiome Project

Integrative Biology at the University of Oxford

Contact Rod Smallwood at r.smallwood at

Go to my Home Page

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Updated 23/04/2010

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