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Computational Modelling of Epithelial to Mesenchymal Transition
Tariq Abdulla1, Lucile Houyel2, Ryan Imms1,
Jean-Marc Schleich3, Ron Summers1
1.Dept Electronic & Electrical Engineering, Loughborough University, UK2. Hospital Marie Lannelongue, Paris, France3. LTSI, University of Rennes 1, [email protected]://www-staff.lboro.ac.uk/~lsrs1 Compucell3D & SBW Workshop 2011
Outline
Introduction Heart Development – what happens?
Anatomy, Tissue, Cell, Protein Current Simulations
In-vitro EMT, Mitosis Future Directions
Introduction
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Heart Development: what happens?
F. Bajolle, S. Zaffran and D. Bonnet, Genetics and embryological mechanisms of congenital heart diseases Archives of Cardiovascular Diseases, Volume 102, Issue 1, January 2009, Pages 59-63
Anatomy
Rear View
Tissue
MyocardiumEndocardium
Cardiac Jelly
Cell
Hign Notch,Low Delta
Hign Delta,Low Notch
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Protein
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Current Simulations
In vitro EMT
Wildtype Notch1 BMP2
L. Luna-zurita et al. “Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation,” The Journal of Clinical Investigation, vol. 120, 2010.
JEC,medium >JECM,medium >JECM,ECM >JEC,ECM >JEC,EC >Jmedium,medium =0
JEC,medium >JECM,medium >JEC,EC >JECM,ECM >JEC,ECM >Jmedium,medium =0
Reduce endocardial cohesion
Reduce endocardial cohesionandIncrease endocardial-ECM adhesion
JEC,medium >JECM,medium >JEC,EC >JECM,ECM >JEC,ECM >Jmedium,medium =0
Mitosis Simulations
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E. J. Armstrong, J. Bischoff, Heart Valve DevelopmentCirculation Research.2004; 95: 459-470
Mitosis Simulations
How does an increase in mitosis prevent EMT from happening?
2D Separation
No Mitosis No MitosisMitosis Mitosis
3D Invasion
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Future Directions
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Create a steppable to calculate the 2D and 3D “TI” of cells in a simulation, and use this to fit simulations to the experimental data
L. Luna-zurita et al. “Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation,” The Journal of Clinical Investigation, vol. 120, 2010.
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More realistic geometry
Compartmental models, polarised cells
AdhesionFlex plugin for levels of VE-Cadherin and Integrin for each cell
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Subcellular SBML model of the regualtion of Snail1 and Snail2 (Slug) by TGFβ and Notch1
Zavadil, J. et al. Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. The EMBO journal. 23, 5, 1155-65 (2004).
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THANK YOU!
Questions?
