This is a Fellowship awarded to Dr Jing-Yi Jeng at the University of Sheffield in 2021. We are co-funding this project with the Dunhill Medical Trust.
Background
Around 1 in 3 of us is expected to experience hearing loss by the age of 50.
Age-related hearing loss is a complex disorder, where symptoms often vary between affected people. It can start to develop as early as the age of 20 or after the age of 60. Affected people may have mild, moderate or severe hearing loss, and it usually gets worse over time. In most cases, age-related hearing loss first affects our ability to detect sounds with high frequencies (or high pitches) – and as many speech sounds are high frequency, it can quickly affect our ability to understand speech, especially in noisy places.
We still do not fully understand why some people lose their hearing with age, and this hinders our ability to develop effective treatments. Many researchers think that age-related hearing loss is at least partly caused by damage to, and loss of, the sound-sensing cells in the cochlea, known as hair cells. These cells are key to transforming sound vibrations in the air into electrical signals that can be processed and perceived by the brain.
Aim
Mutations in a gene called Cdh23 cause an accelerated form of age-related hearing loss in mice and are also linked to hearing loss in people. In this project, Jing-Yi will investigate why and how Cdh23 is involved in age-related hearing loss and why mutations in this gene cause hearing loss to happen faster than normal. She will do this by comparing the structure and function of hair cells from mice with mutations in Cdh23 with those from mice in which the Cdh23 is not mutated.
Jing-Yi will use state-of-the-art experimental approaches such as electrophysiology to measure the electrical activity of the hair cells as they respond to sounds of different frequencies, and electron microscopy, which will allow her to visualise tiny structures within the hair cells. In this way, she will study the impact of the Cdh23 mutations on hair cells in both structural (what do the hair cells, and the structures inside them, look like?) and functional (how do the hair cells respond to sound?) capacities. She will focus in particular on the hair cells that respond to high-frequency sounds, to discover why they are more susceptible to damage from ageing than cells that respond to lower-frequency sounds.
She will also investigate whether gene therapy can reverse the age-related hearing loss seen in the mutant mice by providing their hair cells with a correct copy of the Cdh23 gene. This will be important to provide a proof of concept that it is possible to restore hearing or prevent hearing loss in people with a genetic susceptibility using gene therapy.
Benefit
The findings from this project will further our understanding of age-related hearing loss and may provide an initial proof-of-principle for the future development of gene therapy treatments for hearing loss in humans.