Maintaining hearing: homeostasis in auditory cell function

The inner ear contains some 30,000 cochlear and vestibular sensory hair cells, the mechanoreceptors for hearing and balance respectively. Most sensorineural deafness is caused by loss of hair cell function. Hair cells may fail to develop in genetic diseases, or they may become abnormal or damaged through aging, exposure to loud noise, ototoxic substances (including some antibiotics, chemotherapy), infection, or genetic predisposition. There are limits to the extent to which hair cells can recover from damage; thus many people are permanently affected by hearing loss and balance problems due to permanent loss of hair cells. Mechanisms of homeostasis (maintenance of hair cell function) are likely important in preventing or reversing hair cell damage, but surprisingly little is known of such mechanisms or the molecular networks that confer homeostatic resilience, and how they become overwhelmed by auditory insult. Using the antennal ears of the fruit fly Drosophila melanogaster as a tractable model auditory organ, you will dissect the molecular network that maintains sensitive hearing throughout the fly’s life course and study how this maintenance changes during ageing. You will specifically test the hypothesis that the same molecular networks of sensory cell assembly that bring about the development of the fly’s auditory neurons (about which much is already known) also contribute to their homeostatic control. This will entail analysing the auditory function of flies with adult-specific knockdowns of candidate auditory homeostasis genes, using behavioural, biophysical, and cell imaging assays. The project is part of a larger collaboration with Dr J. Albert at the Ear Institute, UCL: it will entail close liaison with other members of the combined research teams and there will be opportunities for collaborative working visits at the Ear Institute.