Signalling Pathways Driving Cancer Stem Cells: Hedgehog Pathway
Systems Modelling of EMT Cell Signalling Pathways in Heart Valve Development
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Transcript of Systems Modelling of EMT Cell Signalling Pathways in Heart Valve Development
Systems Modelling of EMT Cell Signalling Pathways in Heart Valve
DevelopmentTariq Abdulla1, Ryan Imms1, Jean-Marc Schleich2 and Ron Summers1
VPH 201001/10/2010
1Dept. Electronic and Electrical Engineering, SEIC, Loughborough University, LEICS, UK, LE11 3TUE-mail: [email protected] Web: http://www-staff.lboro.ac.uk/~elta22LTSI, University of Rennes 1, Rennes, F-35000, France
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“Epithelial to Mesenchymal Transition”
Outline
Heart Development – what happens? Heart Looping Neural Crest Cell Migration Endocardial Cushion Growth Congenital Heart Defects
Systems Modelling - how do we do it? Conceptual Model Network Modelling Tissue Modelling Integration
Conclusion and Future Work
Heart Development: what happens?
Rear View
Membranous Septum
Muscular Septum
Neural Crest Cell Migration
Endocardial Cushion Growth
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Systems Modelling – how do we do it?
Different types of computational model are suitable for different levels of biological scale
E.g. Biochemical reactions can be represented as networks or ODEs. Cellular behaviour can be modelled with agent based models.
Use models at one level of scale, to pass information to models at another level of scale
Conceptual Modeling
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Network Modelling
KEGG
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Notch Signalling
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Notch Signalling
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Tissue Modelling Tissues are often modelled as though they
are continuous But many of the interesting things that
happen in tissues are to do with individual cell behaviour, and social behaviour (structure)
When there is an abnormality at tissue level we may need to know whether this is hypotrophic (fewer cells) or hypoplastic (smaller cells)
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Tissue Modelling A lot of the movement of cells around each
other, and how they interact, can be explained by their relative adhesiveness to other cells
This is the Differential Adhesion Hypothesis
Compucell3D
Compucell3D
Integration
We take a proactive approach in model annotation, and are even developing methods for multiscale annotation
This includes combining terms from multiple reference ontologies in post-composition
Use of common formats such as SBML
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Molecules
Cells
Tissues
Organs
?PMR2
Ontologies
Conclusion and Future Work
Modelling systems of such complexity is difficult, but it’s essential if we are to understand them
Comparison with in vivo or in vitro data is essential for model validation and improvement
This project has the potential to be applied to tissue engineering
Questions or suggestions?
Thanks to (in no order):
Ron Summers Ryan Imms Jean-Marc Schleich Fanny Bajolle Lucile Houyel