Measuring mechanosensation during liver organogenesis

Lead Research Organisation: University of Cambridge
Department Name: Physiology Development and Neuroscience

Abstract

Chronic liver failure is a major global health issue, for which the only treatment currently available is organ transplantation. A promising alternative is the use of cell-based therapies, which aim to replace damaged tissue. However, the regenerative cells of the liver are notoriously difficult to maintain outside of the body as the biochemical signals that they require are poorly understood.
Recent evidence suggests that both biochemical and mechanical cues influence liver stem cell fate during development. Therefore, indicating a role of the cell's mechanical environment (a historically overlooked property) in liver development. This project aims to characterise the differentiation of liver precursor cells in response to mechanical tension. With the ultimate goal of elucidating the influence of mechanical properties on liver development.
The mechanical signalling leading to liver precursor differentiation will be investigated to determine how cells respond to mechanical cues. Biological sensors capable of measuring mechanical stress and key developmental pathways will be deployed for this purpose. This will be executed by incorporating fluorescently labelled proteins into stem cells. The stem cells will then be used to produce liver precursor organoids (mini organs in dishes), therefore replicating organ development outside of the body. The mechanical properties of biomaterials known as hydrogels can then be tailored in order to determine the mechanical prerequisites for the self-organisation of cells during liver development. Therefore, allowing for the deduction of the mechanical requirements for liver growth. Understanding these requirements will hopefully influence the production of future cell therapies capable of treating chronic liver failure. Biophysical techniques, such as optical tweezers, will also be used to measure the cell membrane tension, a property known to be influenced by the mechanical environment, in response to the different hydrogels.
This project is aligned to the EPSRC's research areas: "Biomaterials and tissue engineering", "Biophysics and soft matter physics", "Synthetic biology" and "Sensors and instrumentation".

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023046/1 01/10/2019 31/03/2028
2262320 Studentship EP/S023046/1 01/10/2019 30/09/2023 Iona Grace Thelwall