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UK funding (631 213 £) : Développement et entretien de la membrane tectoriale, une matrice extracellulaire de la cochlée nécessaire à une audition normale Ukri01/09/2020 UK Research and Innovation, Royaume Uni
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Développement et entretien de la membrane tectoriale, une matrice extracellulaire de la cochlée nécessaire à une audition normale
| Abstract | Our sense of hearing depends upon the cochlea, a snail shaped organ of the inner ear that contains two types of cell, sensory hair cells and non-sensory supporting cells. While sensory hair cells process sounds entering the ears, the non-sensory cells perform several other key roles, such as providing mechanical support. The hair cells and the supporting cells lie between the basilar and tectorial membranes, flexible strip-like structures than can transmit vibrations caused by sounds along their length. The tectorial membrane is produced by the supporting cells, and it contains two main structures: long, straight, stiff fibrils that resemble uncooked spaghetti and are made of proteins called collagens, proteins which are found throughout the whole body. The collagen fibrils are imbedded within the striated-sheet matrix, a structure made of proteins that are only found in large quantities in the inner ear and form thin sheets that are stacked one upon the other like layers of lasagne. The tectorial membrane is known to be essential for normal hearing, and it works a bit like the lens of the eye. It helps to focus the energy of sound onto the sensory hair cells, the cells that produce the electrical signals our brain perceives, for example, as speech or music. Although the tectorial membrane is known to be critical for normal hearing, how it develops and how it is maintained for life are questions that remain largely unexplored. These questions are important as defects in genes encoding various proteins of the tectorial membrane cause different forms of deafness, some of which start early on in life (suggesting an effect on development), whilst others develop on later in life (suggesting an effect on maintenance). We have recently discovered two proteins in the tectorial membrane that continue to be made after it has finished developing. One of these, a protein called EPYC (pronounced ep-ic), is associated with collagen fibrils in other parts of the body. Although a loss of EPYC early in development causes hearing loss, it is not known if this is due to the loss of EPYC protein from the tectorial membrane or other structures like the basilar membrane. It is also not known if the loss of EPYC causes a form hearing loss that gets progressively worse with age. The other protein is called CEACAM16 (pronounced see-ee-ay-cam16). CEACAM16 is known to be needed for the development of the striated sheet matrix of the tectorial membrane, and its loss causes the remaining non-collagenous matrix to disappear rapidly as animals get older. We do not know, however, if CEACAM16 has to be made all the time to prevent age-related TM degradation. Possibly, if a matrix does not develop normally, it simply does not last very long. CEACAM16 continues, however, to be made in adult animals and presumably for a good reason. To answer these questions about EPYC and CEACAM16, we will use mice in which proteins can be switched off before or after the tectorial membrane has developed. Also, we will use mice in which we can turn on the expression of tectorial membrane proteins as the animals get older to see if this will stop the striated-sheet matrix from degrading as the animals get older. We can do this by simply by adding an activator to the drinking water. The combined outcome of these experiments should help the design of potential strategies for preventing age-related degeneration of the TM, and helping to preserve normal hearing for life. |
| Category | Research Grant |
| Reference | BB/T016337/1 |
| Status | Closed |
| Funded period start | 01/09/2020 |
| Funded period end | 31/08/2024 |
| Funded value | £631 213,00 |
| Source | https://gtr.ukri.org/projects?ref=BB%2FT016337%2F1 |
Participating Organisations
| University of Sussex |
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : University OF Sussex, Brighton, Royaume Uni.
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