In this project, Professor Walter Marcotti at the University of Sheffield seeks to understand how the loss of specific proteins can affect the workings of the sound-sensing cells in the inner ear, leading to hearing loss.
Project start date: April 2019
Project end date: March 2023
Read about the project outcomes here.
About the project
The sound-sensing cells is in the inner ear are called hair cells because they have hair-like structures at the top. When sound enters the inner ear, it causes the hairs to vibrate and starts the process of converting a sound wave into an electrical signal. The signals are then sent to the brain, where they are perceived as sounds like speech and music.
The hair-like structures are arranged in a staircase-like fashion resembling the staggered pipes on a church organ. A large number of proteins are involved in their formation and arrangement. Two of these proteins structures are called myosin 7a and harmonin.
Mutations in the genes for these proteins are associated with Usher syndrome (deaf blindness). In this project, the researchers aim to better understand the role of myosin 7a and harmonin proteins in how the hair-like bundles in hair cells form and work normally. They’ll also study why their loss causes severe-to-profound hearing loss.
How it works
The researchers will assess how well hair cells are working in mice which have been genetically engineered to lack either myosin 7a or harmonin, measuring:
- the tiny electrical currents produced by hair cells when the hairs vibrate
- how well the mice can hear.
Finally, they’ll use microscopy to look at what happens to these hair-like structures when the myosin 7a and harmonin are missing, with the end goal to generate a computer model of hair cells to better understand the roles of myosin 7a and harmonin.
How will this research benefit people at risk of hearing loss?
To develop effective gene therapy approaches to treating hearing loss, we need to have a detailed understanding of the molecules involved in hearing loss.
This project will identify processes involved in the development of Usher syndrome and other types of hearing loss. In the long term, it’ll help to identify molecules in the inner ear that could be targeted by treatments to restore hearing.
What we’ve learned so far
The project led to new insights into the role of myosin 7a, demonstrating that this protein is essential for maintaining the hair-like bundles on top of the hair cells. Without myosin 7a, these structures deteriorate and become more vulnerable to damage from noise.
Understanding these mechanisms is a critical step towards developing treatments for Usher syndrome and other genetic forms of hearing loss.
About the researcher
Walter Marcotti is a Professor of Sensory Neuroscience in the School of Biosciences and co-Director of the Neuroscience Institute at the University of Sheffield. He was awarded an RNID Discovery Research Grant for this project in 2019.
Hearing allows us to communicate with our loved ones and also to indulge in activities such as listening to beautiful music. Hearing loss can therefore isolate people from their surroundings, which can be a devastating feeling. I want to make a difference to people’s lives in this respect, which is the reason why I dedicate my life to providing key knowledge and tools that are required for developing treatments for hearing loss.”
