Investigating the role of internal and external mechanical heterogeneities in tissue morphogenesis

Project ID: 2228cd1335 (You will need this ID for your application)

UCL Lead department: Lab for Molecular Cell Bio

Lead Supervisor: Yanlan Mao

Project Summary:

Our organs must grow to the correct size, shape, and 3D morphology to function correctly. When organ growth is mis-regulated, severe diseases can result. However, the mechanisms behind organ growth control are still not well understand. Studies have shown that heterogeneities in the internal properties of the cells (e.g. cell growth) and their external surrounding extracellular matrix (e.g. ECM mechanics) can result in symmetry breaking events to drive organogenesis.

The Mao lab (LMCB and IPLS) have previously developed a Finite Element Model (FEM) to study tissue morphogenesis (1). The model has recently been further generalised to include various tissue geometries, as well as heterogenous cell and ECM mechanical properties. This makes the model a useful tool to study the independent physical factors for tissue engineering and organ growth control.

The aim of this PhD project is to take a multidisciplinary approach, combining computational physical modelling and experimental tissue biophysics, to explore how internal and external heterogeneities lead to robust symmetry breaking during organ morphogenesis.

You will work with computational biophysicists in the Mao Lab to develop the FEM model, learn the key concepts in biomechanics, as well as using core practices for good software development (version control, automating, testing, documentation), all of which are vital for any career involving computational coding. Knowledge of C++ or Python is an advantage. You will also work with experimental physicists in the lab of Maxim Molodtsov (Crick and UCL Physics) to develop imaging and optic tweezer techniques to measure mechanical properties of cells and the ECM in organoids.

If you have a curious mind, would like to work in a vibrant interdisciplinary lab at the interface of biology and physics, then contact me: y.mao@ucl.ac.uk

Reference:

Tozluoǧlu, M. et al. Planar Differential Growth Rates Initiate Precise Fold Positions in Complex Epithelia. Developmental Cell (2019).