Computational Modelling of Epithelial to Mesenchymal Transition Tariq Abdulla 1 , Lucile Houyel 2 , Ryan Imms 1 , Jean-Marc Schleich 3 , Ron Summers 1 1.Dept Electronic & Electrical Engineering, Loughborough University, UK 2. Hospital Marie Lannelongue, Paris, France 3. LTSI, University of Rennes 1, France [email protected]http://www-staff.lboro.ac.uk/~lsrs1 Compucell3D & SBW Workshop 2011
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
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, UK2. Hospital Marie Lannelongue, Paris, France3. LTSI, University of Rennes 1, [email protected]://www-staff.lboro.ac.uk/~lsrs1 Compucell3D & SBW Workshop 2011
Anatomy, Tissue, Cell, Protein Current Simulations
In-vitro EMT, Mitosis Future Directions
Introduction
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
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.
How does an increase in mitosis prevent EMT from happening?
2D Separation
No Mitosis No MitosisMitosis Mitosis
3D Invasion
22
Future Directions
23
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.
24
More realistic geometry
Compartmental models, polarised cells
AdhesionFlex plugin for levels of VE-Cadherin and Integrin for each cell
25
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).