This is a PhD studentship awarded to Dr Marcela Lipovsek at University College London. Kelly Lo started her PhD in October 2025.
Background
Detection of sound in the inner ear relies on sound-sensing hair cells that transform sound information (a mechanical vibration) into electrical activity that the brain can interpret. Hair cells transmit this electrical information to nerve cells in the inner ear (called spiral ganglion neurons) which carry it into the brain.
It is therefore very important that spiral ganglion neurons in the inner ear are healthy and can faithfully transmit sound information to the brain. Treatments for hearing loss to restore, enhance or replace the work of sensory hair cells will not be effective otherwise. At present, we know very little about how and if spiral ganglion neurons are affected by different types of hearing loss. For example, do they react differently to the damage caused by an ototoxic (ear-damaging) drug than to trauma caused by very loud sounds? How healthy are they in people with genetic forms of hearing loss that affect the hair cells?
Aims
Kelly will investigate what happens to spiral ganglion neurons in different types of hearing loss. They will do this with the goal of identifying new genes or biological processes that could be targeted by tailored treatments to help improve spiral ganglion neuron function and thus hearing.
Research methods
Kelly will carry out an in-depth assessment of all genes that are active in individual spiral ganglion neurons, using a state-of-the-art technique called single nuclei RNA sequencing. They will study spiral ganglion neurons from mouse models that represent three types of hearing loss which are the current focus of treatment development:
- Mice that lack the ‘Otof’ (otoferlin) gene, that is needed for the transmission of sound information from hair cells to spiral ganglion neurons. Gene therapies for otoferlin-linked deafness are currently being tested in clinical trials in people.
- Mice treated with aminoglycoside antibiotics; these are used in the clinic to treat serious and persistent infections, but can damage hair cells as a side effect, causing permanent hearing loss.
- Mice exposed to high levels of noise that damage hair cells and their contacts with spiral ganglion neurons.
Kelly will compare patterns of gene expression in the spiral ganglion neurons between these different mouse models of hearing loss, and against mice with normal hearing.
Benefit
This work will allow the identification of new genes or biological processes that could be directly targeted with therapeutics in the near future. This could lead to improved cochlear implant outcomes, improved prevention of hearing loss caused by ototoxic medications, improved treatment of noise-induced hearing loss, and/or improved effectiveness of gene therapies that restore hair cell function and thus hearing.