Computational Modelling of Epithelial to Mesenchymal Transition

Tariq Abdulla1, Ryan Imms1, Jean-Louis Dillenseger2,3,

Jean-Marc Schleich2,3, Ron Summers1

1.Dept Electronic & Electrical Engineering, Loughborough University, UK

2. LTSI, University of Rennes 1, France

3. INSERM, U642, Rennes, F-35000, France

R.Summers@lboro.ac.uk

http://www-staff.lboro.ac.uk/~lsrs1

Outline

• Introduction to the team

• Heart Development

• Multiscale Modelling

• EMT Simulations

International Team

Heart Development

How … from …To …

Primitive heart tube Heart at the end of development

Epithelial to Mesenchymal Transition

Notch Delta

Muscular Septum

Membranous Septum

Nature

Multiscale Modelling

Modelling Scales

Hunter P, Robbins P, Noble D (2002) The IUPS human physiome project.Eur J Physiol 445 1-9

EMT 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.

CPM Model

22

',))'(()),(())'(()),(( )()()1( VvSsJE vs

xxxxxx

Compucell3D

Mitosis Simulations

Mitosis Simulations

How does an increase in mitosis prevent EMT from happening?

2D Separation

No Mitosis No MitosisMitosis Mitosis

3D Invasion

Thank you for your attention

Any questions?

Validation Step

Our simulations are not validated but we intend to do this.

To illustrate how this can be done, here is an existing example of a

validated simulation.

Somitogenesis