Investigating mechanotransduction in the mouse cochlea
Lead Research Organisation:
University College London
Department Name: Structural Molecular Biology
Abstract
Stratic Research Priority: Bioscience for Health
Abstract
Mechanoelectrical transduction is the crucial event of the auditory system. Within the bony fluid-filled structure of the cochlea, auditory hair cells detect mechanical stimuli elicited by sound waves entering the ear by submicron deflections of the stereociliary bundles. The mechanotransducer channel converts a mechanical stimulus into an electrical signal. The structure of this channel is unknown and the gating mechanism is unclear. Previous work has been done in isolated cells and there are few studies on mature mammalian models. We aim to identify the properties of this channel and mechanism of function in mature mammalian hair cells.
Project
The mechanotransducer (MET) channel has been of long standing interest to auditory physiologists. The molecular structure of this channel, however, remains unknown and the mechanism of opening unclear. The MET channel is found at the tips of stereocilia, grouped in a hair bundle-the inner ear's mechanosensitive organelle. Conventionally, it was proposed that the MET channels gating mechanism is tightly coupled with extracellular tip links that connect the tips of shorter cilia to the sides of their taller neighbours. Hence the deflection of a hair bundle towards the tallest cilia would result in the opening of the channel, whereas a push in the opposite direction would promote channel closing. Currently, this conventional view is being disputed as new research has found that a MET current can be elicited when the connections between the tip links and the stereocilia are severed and a current of reverse polarity can be induced when pushing the cilia towards the smallest cilia. The main aim of this project is to investigate the properties of this channel with a particular interest in deciphering its gating mechanism and function. This project will also involve developing novel techniques to be able to investigate the MET channel within extracellular explants of mature mammals.
Abstract
Mechanoelectrical transduction is the crucial event of the auditory system. Within the bony fluid-filled structure of the cochlea, auditory hair cells detect mechanical stimuli elicited by sound waves entering the ear by submicron deflections of the stereociliary bundles. The mechanotransducer channel converts a mechanical stimulus into an electrical signal. The structure of this channel is unknown and the gating mechanism is unclear. Previous work has been done in isolated cells and there are few studies on mature mammalian models. We aim to identify the properties of this channel and mechanism of function in mature mammalian hair cells.
Project
The mechanotransducer (MET) channel has been of long standing interest to auditory physiologists. The molecular structure of this channel, however, remains unknown and the mechanism of opening unclear. The MET channel is found at the tips of stereocilia, grouped in a hair bundle-the inner ear's mechanosensitive organelle. Conventionally, it was proposed that the MET channels gating mechanism is tightly coupled with extracellular tip links that connect the tips of shorter cilia to the sides of their taller neighbours. Hence the deflection of a hair bundle towards the tallest cilia would result in the opening of the channel, whereas a push in the opposite direction would promote channel closing. Currently, this conventional view is being disputed as new research has found that a MET current can be elicited when the connections between the tip links and the stereocilia are severed and a current of reverse polarity can be induced when pushing the cilia towards the smallest cilia. The main aim of this project is to investigate the properties of this channel with a particular interest in deciphering its gating mechanism and function. This project will also involve developing novel techniques to be able to investigate the MET channel within extracellular explants of mature mammals.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M009513/1 | 01/10/2015 | 31/03/2024 | |||
| 1627184 | Studentship | BB/M009513/1 | 01/10/2015 | 30/09/2019 | Assel Kashkenbayeva |