Hair cell production and regeneration
The Inaugural Deafness Research UK UCLEI Research Fellowship was awarded to Dr Nico Daudet at the UCL Ear Institute in London to investigate the role of the protein Notch in the inner ear.
[Fellowship: 2006-2009]
Eighty-seven percent of the UK’s 9 million cases of hearing impairment are caused by damage to the inner ear (the cochlea). This type of hearing loss is known as sensorineural deafness and is characterised initially by a high-frequency hearing loss, which affects the ability to hear and understand speech.
Sensorineural deafness results mainly from damage to cells in the inner ear known as "hair" cells. These highly complex sensory cells – so called because of the tiny hair-like bundles at their tips – detect sound vibrations, which are passed from the outside world via the eardrum and the bones of the middle ear, to the cochlea. Here they are converted by the hair cells into electrical signals that can then be processed and understood by the brain.
In humans, the loss of hair cells is irreversible and results in permanent deafness. However in birds, hair cells are regenerated spontaneously and throughout adult life. The regeneration of hair cells could be used as a therapy for certain forms of human deafness, but developing efficient and safe cures relies on a better understanding of the molecular signals involved in hair cell formation and regeneration.
The aim of the project is to investigate this question in the chick inner ear and, in particular, to study the function of the protein Notch. formation of hair cells and their precursors.
Elena Chrysostomou – a Medical Research Council-funded PhD student – is about to complete her second year in the lab, working with Dr Daudet. She is using a combination of imaging techniques to monitor the variations of Notch activity in the developing chick inner ear. Elena’s experiments have thus far enabled the research team to see dynamic changes in the level of the marker in a region of the inner ear called the otic cup.
Post-doctoral researcher Dr Steve Freeman started working with Dr Daudet in February 2008 and is investigating the function of a family of genes known as Sox genes in inner ear development. One gene that is essential for the formation of the sensory progenitors which give rise to hair cells in the ear is named Sox2, and Steve is currently testing whether Notch signalling interacts with Sox2 (as well as additional members of the Sox family) during hair cell production.
In collaboration with Dr Jennifer Stone (Seattle, USA), Dr Daudet has begun to study the role of Notch signalling in hair cell regeneration. In the inner ear of the chick, regeneration occurs spontaneously after hair cell damage, because the supporting cells can act as progenitors for new hair cells throughout life. The supporting cells can either directly convert into hair cells, or proliferate and give rise to both new hair cells and new supporting cells. The latter type of regeneration is particularly important to restore a correct number of cells following damage.
Dr Daudet’s research projects investigate the molecular mechanisms of hair cell development and regeneration; a direct application of the findings could be the development of new therapies for certain forms of human deafness, based on hair cell regeneration.
