PhD studentship – Modelling Shape Generation by the Basement Membrane

Deadline: 6^th May 2024, apply here: https://www.exeter.ac.uk/study/funding/award/?id=5112

Project overview

Morphogenesis is a biophysical process where cellular forces guide complex cellular deformations that shape animal tissues and organs. Understanding the relevant forces and how they act on and deform biological tissues is challenging due to the complex, anisotropic material properties of cells and the extracellular matrix (ECM) surrounding them. The basement membrane (BM), a sheet-like ECM, is essential for guiding epithelial morphology. We recently demonstrated that insufficient BM growth results in geometric frustration, accumulation of elastic pre-stresses and tissue deformation. While pre-stress resides in many biological tissues, the conditions under which pre-stress arises and how they feed back on tissue morphology remain unclear.

This interdisciplinary PhD, spanning physics, mathematics, computing and biology, investigates pre-stress, arising from the mechanical interplay between tissue and BM growth, as a universal mechanism of biological shape generation. In close collaboration with experimentalists, the project will yield a ‘data-informed’ universal modelling framework paving the road for understanding the biomechanics of shape generation in animal development, disease and synthetic systems.

This project is funded by the University of Exeter Engineering and Physical Research Council (EPSRC) Doctoral Training Partnership and the successful applicant will join the groups of Dr. Stefan Harmansa (experiments) and Dr. David Richards (theory).

Main objectives

1. Create a novel modelling framework to simulate the growth of tissues (via continuum and vertex-modelling) along with their surrounding BM (via continuum and lattice modelling).
2. Incorporate growth and mechanical anisotropies to give a sophisticated description of the complex material properties of BMs.
3. Identify how geometric frustrations arise during growth, leading to elastic pre-stress that guides complex tissue shapes.
4. Challenge modelling frameworks in different epithelial systems (Drosophila, zebrafish and organoids) yielding a universal framework to predict tissue morphology based on growth dynamics and material parameters.

Broader impact

Shape and function are inherently linked entities as alterations in morphology can lead to malfunction and disease. This project will yield unprecedented insight into biological shape generation and the mathematical model will provide a powerful tool to understand animal development and for tissue engineering approaches designing custom tissue shapes.

Application

For more information and discussion of the project please contact Stefan Harmansa (s.harmansa@exeter.ac.uk) and check our lab webpage.

Apply here: https://www.exeter.ac.uk/study/funding/award/?id=5112