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Regulation of cell division by mechanical force in 3D tissue environments


   Faculty of Biology, Medicine and Health

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The cells and tissues of our bodies are constantly being pushed and pulled and it is vital that they sense and respond to these mechanical forces appropriately to maintain normal tissue function1. Whilst we are beginning to understand some of the cellular mechanisms that link cell behaviour with mechanical force in isolated cells, we know much less about how this applies to the complex tissues of our bodies. Bridging this gap is important considering the significant mechanical changes that take place in tissues as they are formed and shaped in the embryo and as they age and become diseased (e.g. via cancer) in the adult.

In this project, we will investigate how fundamental cellular functions – cell division and cell motility – are regulated by mechanical force in a complex embryonic tissue. In recent work, we have shown that epithelial cells are exquisitely sensitive to stretching (tensile) force, which increases their cell division rate and reorients divisions along the axis of stretch2. For this PhD project, we will build on these findings to determine how mechanical force regulates cell behaviour across multiple layers of a 3D tissue. In pilot work we find that that cells in different regions of the same tissue can have fundamentally different responses to the same force, suggesting that the local tissue environment, and especially cell adhesion, plays a crucial role in regulating mechano-response.

For their PhD, the student will:

1. Use light sheet fluorescent microscopy to live image cell division and cell motility in stretched and unstretched tissue.

2. Develop/apply mathematical modelling to understand patterns of mechanical force in tissue3,4.

3. Construct chimeric tissues to perturb local adhesive environments.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website).

References

Heisenberg, C. P. & Bellaiche, Y. (2013) Forces in tissue morphogenesis and patterning. Cell 153, 948-962.

Nestor-Bergmann, A., Stooke-Vaughan, G.A., Goddard, G.K., Starborg, T., Jensen, O.E. and Woolner, S. (2019) Decoupling the roles of cell shape and mechanical stress in orienting and cueing epithelial mitosis. Cell Reports 26: 2088-2100.

Nestor-Bergmann, A., Goddard, G., Woolner, S. and Jensen, O.E. (2017) Relating cell shape and mechanical stress in a spatially disordered epithelium using a vertex-based model. Mathematical Medicine and Biology. 35 (Supplement 1) 1-27

Jensen, O.E., Johns, E. and Woolner, S. (2020) Force networks, torque balance and Airy stress in the planar vertex model of a confluent epithelium. Proceedings of the Royal Society A, 476: 2237.

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