Cell polarity and mechanical regulation in epithelia – a genetic and biophysical analysis

• Funding – self-funded/externally sponsored applicants   (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

It is well-established now that during development biochemical parameters as well as mechanical cues are important to generate patterning and morphogenesis. In epithelial tissues for instance, cells can control their shape by subcellular alterations of force production. When such changes are locally coordinated across groups of cells, collective cell shape changes drive morphogenesis. During development the level of tension and stress in tissues can affect the proliferation of cells within, the fate of cells and the shape of organs. Furthermore, cells in certain diseases alter their mechanical properties raising the question of how epithelial tissues control their tension. 

Central question 

A defining feature of epithelial cells is that they are polarised. The establishment of apico-basal polarity is driven by protein complexes that are conserved between flies and humans and important for the physiological roles of the epithelium. Our lab recently found that the cell polarity machinery impacts the mechanical properties of epithelial cells corroborating links in the literature suggesting that biochemical cues from the cell polarity machinery and contractility regulation are highly coupled. However, the molecular nature of this regulation is unclear and will be addressed in this project. 

Approach 

Non-muscle myosin II (myosin II) is a motor protein that drives contraction of the actin cytoskeleton and generates force. The pathways leading to myosin II activation are well understood, yet the mechanisms that suppress it, less so. In this project the mechanisms repressing myosin II activity in Drosophila will be studied to better understand tension regulation in epithelial cells. Key questions in cell and developmental biology are how these actomyosin behaviours are triggered and what physiological outputs they drive. Actomyosin is further a prime example of an active gel and understanding its properties and behaviours is of central importance in physics of active, out of equilibrium systems.  

Drosophila has been instrumental in revealing the genes that operate in the pathways that lead to myosin II activation due to its genetic tractability, the possibility to perform quantitative live cell imaging and the generation of transgenic fly lines allowing targeted testing of hypotheses. This type of data naturally lend itself to modelling and biophysical analysis. 

Nature of project and training opportunities 

In this interdisciplinary project at the interface of cell biology, developmental biology and biomechanics you will use genetics, chemical genetics and opto-chemical genetics, state of the art laser scanning confocal microscopy and image analysis and biophysical approaches to study how cell polarity regulates mechanical parameters of epithelia in the fly. The study will explore upstream regulatory mechanisms linking actomyosin regulation to cell mechanics and polarity, offering insights into feedback and regulation. The methods applied in this project are highly transferable, therefore training on this project will enable you to proceed a career in academia as well as industry.  

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research.  We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.