This is a Fellowship awarded to Dr Elisa Martelletti at King’s College London, in 2023. We are co-funding this fellowship in partnership with the Dunhill Medical Trust.
Background
Hearing loss is the most common form of sensory loss in people of all ages. It can have a significant impact on quality of life, affecting speech and language development, communication, and learning. Although hearing loss is estimated to affect one in every five people in the UK, there are no effective treatments that can prevent or stop its progression or restore lost hearing. We need to better understand the molecular processes that underlie hearing loss to be able to design better, more effective treatments.
If a part of the body becomes damaged, whether through trauma or another cause, the body’s first response is inflammation, which is triggered by the immune system. There is a delicate balance between the initial (called acute) activation of inflammation and its subsequent deactivation once the danger has passed or the damage has been repaired. If inflammation is left unchecked, it becomes chronic (long-lasting) and can cause severe damage to the affected tissue.
Inflammation is controlled by specific cells in the immune system, including key cells like macrophages, and by the body’s production of pro- and anti-inflammatory molecules. However, we don’t have a good understanding of the inflammatory response in the cochlea – the hearing organ in the inner ear – and how much it might contribute to the development of hearing loss.
Aims
In this project, Elisa will determine whether inflammation within the cochlea causes hearing loss directly or whether it is a response to damage in the cochlea that causes hearing loss – that is, it is a response to hearing loss. To do this, Elisa will study mice which carry changes in one of two genes that are involved in the inflammatory response, called ‘Acsl4’ and ‘Pex3’.
Both types of mice develop progressive hearing loss and are studied as models of age-related hearing loss, so will allow Elisa to study inflammation in the context of hearing loss. She will investigate the type and number of immune cells, as well as the presence and levels of pro- and anti-inflammatory markers and molecules that are present in the cochlea of mice.
Elisa will also study macrophages in more detail – as they change their shape during the inflammatory response, studying them will provide more information about their role in inflammation in the cochlea. Finally, she will compare the two mouse models of progressive hearing loss to see if they have the same, or a different, inflammatory response
Benefit
Overall, this project will yield new information that may improve our understanding of the processes that underlie progressive hearing loss. People with hearing loss will benefit from a better understanding of how inflammation is controlled within the cochlea, and the findings may ultimately lead to the development of new treatments that target inflammation and in doing so prevent, delay, or reduce hearing loss.