Current challenges

Current challenges to modeling in Systems Biology include those associated with issues of complexity and representing systems with multi-scale attributes. For example a drawback of current modelling approaches, including Petri nets, is their limitation to relatively small networks.

Biological systems can be represented as networks which themselves typically contain regular (network) structures, and/or repeated occurrences of network patterns. The networks are also often organised a hierarchical manner, reflecting the physical and spatial organisation of the organism, from the intracellular to the intercellular level and beyond (tissues, organs etc.). Examples of organisation at the intracellular level include: cytosol, nucleus, ribosome, vesicles, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, vacuoles, and lysosomes.

Although network models can be designed using standard Petri nets, so far there is no dedicated support for such structuring; it becomes impractical as the size of the networks to be modelled increases.

  • Besides the purely technical aspect due to the impracticality of handling large flat nets, humans need some hierarchy and organisation in what they are designing in order to be able to conceptualise the modelled object.
  • Thus, models should explicitly reflect the organisation in complex biological systems.

There are two established orthogonal concepts in Petri net modelling to manage large-scale networks - structuring by hierarchies and colours. However, their potential for BioModel Engineering (BME) has not been systematically explored so far.

The aim

The aim of this project is to develop a theory and associated methodology to support the modelling of large and complex multiscale biological systems by the use of hierarchically coloured Petri nets.

The objectives

1. The compilation of a set of features that are better modelled in Petri nets using hierarchy and colour than without these attributes, and gathering a set of corresponding biological examples to drive the development of the theory and methodology, which will be made available to the scientific community. The general features to be investigated here include localisation, mobility and consequently communication. In addition notions of structural abstraction will be considered

2. Develop a theory development for the true integration of hierarchy and colour in a sound manner. Concepts that we wish to incorporate into the theory include: multiple colouring of tokens and the dynamic assignation of colours, potentially dynamically assigned colour palettes on places, a hierarchical, possibly object-oriented structure over colours, operations over colours including intensities, encoding of priorities, inheritance over colours from ‘templates’.

3. Create a set of design methodologies for the application of hierarchically coloured nets to multiscale biological problems. Attributes will include spatial information (for instance agent-based, grid oriented), and membranes with dynamic compartments.

4. Develop a methodology and set of associated techniques for the analysis of such multiscale models, to take into account spatial and hierarchical aspects.

5. Hold workshops and outreach activities, including workshops at Brunel on the use of Petri nets in Systems Biology, and multiscale modelling approaches in Systems Biology.

Note that objective 4 – analysis techniques – was added at the suggestion of one of the project reviewers, and in order to achieve this in the timescale, we removed the original objective regarding automatic folding which was of lower priority.

latest update: December 06, 2011, at 12:42 AM