Project Reference: TRG27-PDN-EP1

Project title: Robustness and Plasticity of Epithelial Cell Shapes

Project outline

Precise control of cell shape is key to cell function. Animal cell shape is the result of forces at the cell surface, mostly generated by actin networks and cellular adhesions, balanced by the resistive forces of cytoplasmic structures. As such, understanding how cell shape is controlled requires cross-disciplinary approaches, combining biology with physics and modelling.

A particularly important example of tight shape-function coupling is found in epithelial cells, which form sealed, protective sheets between the organism and the external world. Epithelial cells display a variety of shapes generally classified into squamous, cuboidal and columnar. Furthermore, epithelia can display single-layered or multi-layered tissue architectures. These diverse shapes and architectures are tightly connected to specific epithelial functions. Yet, the mechanisms controlling the establishment, maintenance and dynamics of epithelial cell shapes and tissue architectures are poorly understood.

In the proposed project, the student will investigate the mechanical and molecular mechanisms controlling epithelial shapes in induced pluripotent stem cell (iPSCs). Past work from the lab showed that iPSCs form epithelia of different heights when cultured on substrates of different stiffnesses. The student will develop a cross-disciplinary approach combining biomechanics, advanced imaging and stem cell biology and work in collaboration with theorists, to investigate how iPSC epithelial morphologies are controlled and how transitions between different epithelial architectures are regulated. We will then investigate how iPSCs change morphologies during epithelial-to-mesenchymal transition associated with iPSC differentiation. 

Together, the project will shed light on the mechanisms controlling epithelial organisation, and interrogate the cross-talk between cell shape and fate during early differentiation in iPS cells.

Principal Supervisor

Professor Ewa Paluch

Email address: ekp25@cam.ac.uk

Department / Partner Institute: Physiology, Development and Neuroscience (PDN)

Website: https://paluchlab.uk

BBSRC strategic theme

Understanding the rules of life