Abdulla compucell3d workshopPresentation Transcript
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, UK 2. Hospital Marie Lannelongue, Paris, France 3. LTSI, University of Rennes 1, France T.Abdulla@lboro.ac.uk http://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
4 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 Cardiac Jelly Endocardium Myocardium
Cell Hign Delta, Low Notch Hign Notch, Low Delta
13 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.
20 E. J. Armstrong, J. Bischoff, Heart Valve Development Circulation Research.2004; 95: 459-470
Mitosis Simulations How does an increase in mitosis prevent EMT from happening? No Mitosis Mitosis No Mitosis Mitosis 2D Separation 3D Invasion
22 Future Directions
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.
More realistic geometry
Compartmental models, polarised cells
AdhesionFlexplugin for levels of VE-Cadherin and Integrin for each cell
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).