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How do cells sense mechanical loading?
This project will investigate how cells sense mechanical loading and how sensing can be altered with ageing or tissue degeneration. The project is interdisciplinary and includes engineering and biology aspects. The thematic emphasis can be adjusted to the student's background and interests.
Mechanical loading is an important external cue that is needed to maintain the functionality of mechanosensitive tissues. For muscle, the role of mechanical stimulation is quite obvious, but many other musculoskeletal tissues also depend on receiving appropriate mechanical cues. The intervertebral disc for example is subjected to strain and compression during daily activity and both are important in maintaining nutrition and tissue balance. If loading is however too excessive or too little, detrimental degenerative changes can occur in the tissue. Despite the obvious role of mechanical loading, the mechanisms of mechanosensing, i.e. how cells sense loading and respond in an appropriate manner, are still not clear. In this project, a novel class of mechanosensitive channels (TRP channels) and their role in the intervertebral disc will be investigated.
Mechanical loading is an important external cue that is needed to maintain the functionality of mechanosensitive tissues. For muscle, the role of mechanical stimulation is quite obvious, but many other musculoskeletal tissues also depend on receiving appropriate mechanical cues. The intervertebral disc for example is subjected to strain and compression during daily activity and both are important in maintaining nutrition and tissue balance. If loading is however too excessive or too little, detrimental degenerative changes can occur in the tissue. Despite the obvious role of mechanical loading, the mechanisms of mechanosensing, i.e. how cells sense loading and respond in an appropriate manner, are still not clear. In this project, a novel class of mechanosensitive channels (TRP channels) and their role in the intervertebral disc will be investigated.
The goal of this project is to characterize the expression of TRP channels in the intervertebral disc and to determine their changes with age and degeneration. The involvement of these channels in responding to mechanical and osmotic loading will also be investigated. For this, bioreactors and cell stimulation devices to apply strain, compression or hydrostatic pressure to cells will be used. Students can either work on the engineering side (by working on the cell stimulation devices) or on the biology side (by analyzing the cellular responses to mechanical loading and investigate whether these depend on TRP channels). The experimental set-up will – according to the subproject – contain gene/protein expression analysis, inhibitor studies, knockdown studies or mechanical testing.
Tasks: 10% literature review, 80% experimental work (with help from team members) and 10% preparation of report and presentation.
The goal of this project is to characterize the expression of TRP channels in the intervertebral disc and to determine their changes with age and degeneration. The involvement of these channels in responding to mechanical and osmotic loading will also be investigated. For this, bioreactors and cell stimulation devices to apply strain, compression or hydrostatic pressure to cells will be used. Students can either work on the engineering side (by working on the cell stimulation devices) or on the biology side (by analyzing the cellular responses to mechanical loading and investigate whether these depend on TRP channels). The experimental set-up will – according to the subproject – contain gene/protein expression analysis, inhibitor studies, knockdown studies or mechanical testing. Tasks: 10% literature review, 80% experimental work (with help from team members) and 10% preparation of report and presentation.
Dr. Karin Wuertz-Kozak, kwuertz@ethz.ch / Institute for Biomechanics, HPP O12, ETH Zürich / Professorship Wuertz-Kozak
Dr. Karin Wuertz-Kozak, kwuertz@ethz.ch / Institute for Biomechanics, HPP O12, ETH Zürich / Professorship Wuertz-Kozak