Research group: Scientific Computing for Systems Biology (MAS3.2).
Coordinator of the Silicon Cell Initiative Amsterdam: Hans V. Westerhof, IMBW
The Silicon Cell Initiative Amsterdam aims at computing Life at the cellular level, on the basis of our rapidly expanding knowledge of a cell's genetics, biochemistry, and molecular dynamics. Four Amsterdam-based research institutes have formed a Consortium to realise this aim, which is expected to take decades. CWI's involvement concerns the analytic and numerical study of models, system reduction of dynamic systems for biochemical reaction networks, and visualization and virtual reality research.
Why the SiC initiative?
The knowledge at the genetic level, at the biochemistry level and at the molecular mechanistic level is expanding rapidly. These developments make it possible to strive for a fundamental and quantitative understanding of the cell. If the cell can be approached in a rational and integrated way, it can be utilized as a "cell factory" to produce chemicals or pharmaceutical components.
In contrast to many international initiatives aiming at whole-cell simulation which are mainly based on bio-informatics, SiC aims at doing science in the sense of a "systematic study in which experiment and theory go hand in hand". Rather than a qualitative understanding of the principles of cell function, SiC will calculate the implications for cell functioning based on real experimental data and mathematical models. Mathematics Some of the mathematical and computational requirements concern the application of already existing techniques, including the analysis and numerical solution of ordinary and partial differential equations, parameter estimation in non-linear dynamical systems, and graph theory. New challenges concern the interaction between phenomena involving a wide range of scales (both in space and in time) and organisational complexity, the incorporation of uncertainty into the models, and the discovery of principles to reduce the size of the problem without losing essential information.
CWI People involved
- Maksat Ashyraliyev
- Joke Blom
- Maciej Dobrzyński
- Arjen Doelman
- Luca Ferracina
- Mark Peletier (now at TU/e)
- Jan Verwer
- Robert van Liere, INS3
- Jan van Schuppen
Projects within the context of SiC
Mathematics and Computation for the System Biology of Cells
The aim of the project is to develop, implement, and validate mathematical and computational techniques for the systems biology of the cell. Depending on the cellular phenomenon considered, models and methods of appropriate temporal and spatial scales will be developed and can then be applied, a.o. multi-adaptive computational methods for PDEs for moderate spatial and temporal variability within a cell or an organelle; and methods for integration of different approaches into a single simulation.
Simulation of developmental regulatory networks
In this project we will develop a model for simulating regulatory networks that are capable of quantitatively reproducing spatial and temporal expression patterns in developmental processes. Mathematically speaking this amounts to continuum-discrete hybrid models where discrete, moving and deformable objects in which biochemical reactions take place exchange species with the surrounding environment modelled as a continuum in which species diffuse and decay.
Mesoscale simulations paradigms in the Silicon Cell
Reaction-diffusion phenomena on dynamically changing complex-shaped surfaces represent an important class of problems relevant to a wide range of applications in the natural sciences. In this project we compare two different model approaches in the mesoscopic regime: using particle-based methods (lattice Boltzmann) and using methods based on PDEs (adaptive grid).
Continuum modelling of biological membranes
Recent modelling of biological membranes on a continuum basis leads to a mesoscopic description of membrane behaviour, resulting in partial differential equations with a computationally expensive nonlocal component. These are being studied, again from a combined numerical-analytical viewpoint.
- IMBW (Institute for Molecular Biological Sciences; Vrije Universiteit)
theoretical and experimental molecular biology
- SILS (Swammerdam Institute for Life Sciences; University of Amsterdam)
www.science.uva.nl/research/sils/research/str/ theoretical and experimental molecular biology
- SCS (Section Computational Science; University of Amsterdam)
applied and numerical mathematics, control and system theory, visualization