Prof. V. Danos (Edinburgh, UK), about the talk;
Prof. D. Gilbert (Glasgow, UK), about the talk;
Prof. P. Hogeweg (Utrecht, The Netherlands), about the talk;
Dr. M. Kirkilionis (Warwick, UK), about the talk;
Dr. F. J. Romero-Campero (Nottingham, UK), about the talk;
Prof. S. Wolfram (Champaign - IL - USA), about the talk.
Prof. V. Danos
A stochastic calculus of binding with applications to the modelling of cellular signalling
Kappa is a stochastic calculus of binding and modification that handles well the modelling of complex and fine-grained regulation in biological systems. Its main usage is in the description, simulation and causal dissection of signalling pathways -where traditional methods are beset by combinatorial explosion and do not offer the same ease of description
Prof. D. Gilbert
Modelling and analysing the dynamic behaviour of biochemical networks
Modelling intracellular biochemical networks presents particular challenges
connected with the need to reconcile the difficulty of obtaining
experimental data with the requirements of providing information at a level
of detail which will be useful for biochemists. Such models should be able
to both explain and predict behaviour, and I will illustrate this with
research undertaken in Glasgow in the area of intracellular signalling
pathways. Moreover modelling is a key component in the emerging discipline
of Synthetic Biology in which the activity of design as well as analysis is
of prime importance. I will discuss a framework for modelling and analysing
biochemical networks which unifies qualitative and quantitative approaches,
and show how it has been applied in the context of a Synthetic Biology
project. I will also describe a very fast model checker that has been
developed at Glasgow which can be applied to biochemical systems and discuss
how it can be used to drive the design of such systems.
Prof. P. Hogeweg
Multilevel modeling of morphogenesis
In order to study the growth and development of cellular systems one needs a formalism in which on can combine the biophysical properties of cells with the
modulation of these properties by gene regulatory processes.
I will argue that the multisclale CA formalism now known as the Cellular Potts Model (CPM) provides a simple yet basically sound representation of a biological cell, which can be interfaced with gene regulatory processes.
It represents a cell as highly deformable object which
takes its shape from internal and external forces acting upon it.
I will demonstrate how within this formalism
complex large scale morphodynamic processes can result from local regulation
of cell, and in particular membrane, properties.
I will explain morphogenetic mechanisms which tend to evolve in such systems.
Dr. M. Kirkilionis
Multi-Scale Modeling and Simulation of Cellular Membrane Transport and Reaction Systems
Based on the development of new experimental techniques, mainly imaging
techniques like FRAP and FRET, cellular transport and reaction processes
can be better understood than ever before. Cell biology in general
offers a whole range of such important applications (in the end all life
depends on this complex machinery) which are challenging for
mathematical modeling and the performance of existing numerical
algorithms. Inside the cell membrane systems like the ones involved in
the secretory pathway are especially important and can be used to
understand the state-of-the-art of modeling and simulation in a wider
area to much advantage.
One specific property of cellular structures are their complicated
geometry, here just called 'Complex Domains'. The complexity of these
cellular domains can now be measured much more accurately with the help
of modern imaging and image analysis techniques. It is tempting to
combine methods from image analysis and numerical simulations in order
to get a better understanding how different molecules, small to large
(ions to protein complexes) distribute and react inside the cell.
Moreover such geometries are typically 'complex' on every relevant
scale. This makes their representation in a simulation typically
difficult, and one must use adequate approximations. This need for
averaging nicely explains why (in this case spatial) scales are
important (and why all modeling is relative to a chosen scale), and
therefore scale is perhaps the most important notion in this area, even
before considering the appropriate choice of either a discrete or
continuous state space to represent the different components of the
The same is true for the second part of the problem, the action (mostly
binding) of macro-molecules with each other or other binding partners.
This process creates events at which the system state changes, and that
again needs to be represented relative to a chosen temporal scale in the
model (and finally the simulation). We discuss this with the help of
birth-death processes and the dynamics of Markov chains, and describe
the dynamics of ion channels in a typical membrane with the help of
Dr. F. J. Romero-Campero
A Multiscale Modelling Framework Based On P Systems
Cellular systems present a highly complex organisation at
different scales including the molecular, cellular and colony levels. The
complexity at each one of these levels is tighly interrelated to each other.
Integrative systems biology aims to obtain a deeper understanding of
cellular systems by focusing on the systemic integration of the different
levels of organisation in cellular systems.
The different approaches in celluar modelling within systems biology
have been classified into mathematical and computational frameworks.
Specifically, the methodology to develop computational models has been
recently called executable biology since it produces executable algorithms
whose computations resemble the evolution of cellular systems.
In this work we present P systems as a multiscale modelling framework
within executable biology. P system models explicitly specify the molecular, cellular and colony levels in cellular systems in a relevant and understandable manner. Molecular species and their structure are represented
by objects or strings, compartmentalisation is described using membrane
structures and finally cellular colonies and tissues are modelled as a collection of interacting individual P systems.
The interactions between the components of cellular systems are described using rewriting rules. These rules can in turn be grouped together
into modules to characterise specific cellular processes.
One of our current research lines focuses on the design of cell systems biology models
exhibiting a prefixed behaviour by assembling automatically these cellular modules. Our approach is equally applicable to systems as well as
Prof. S. Wolfram
The View from A New Kind of Science
to be defined