Beta-dystroglycan is a protein found in muscle and other cell types. It is found in the outer layer of the cell, the cell membrane, which separates the inside of the cell from the outside environment and controls what can get into and out of the cell. Beta-dystroglycan forms part of a larger structure of proteins called the dystroglycan complex that allows cells to contact the outside world, both mechanically and chemically. As the inner ear detects sounds, which are mechanical vibrations in the air, this requires precise communication between structures outside of the cells and structures inside the sensory hair cells themselves. This suggests that dystroglycan complexes could be involved in hearing but until recently, beta-dystroglycan had not been detected in the inner ear.
Recently, the researchers at Sheffield found that a naturally-occurring modified version of beta-dystroglycan is present at very high levels in the inner ear – it had not been detected previously due to this modification. The modification changes how beta-dystroglycan interacts with other proteins, including which proteins it actually interacts with, and changes how cells talk to each other and what they let into and out of the cell. This modified version of beta-dystroglycan in the inner ear could be important for hearing, so understanding more about it and what it does could provide a greater understanding of both noise-induced and age-related hearing loss.
Adam will study the modified version of beta-dystroglycan in the inner ear to better understand the importance of the dystroglycan complex in hearing. He will investigate which specific types of cell in the inner ear produce beta-dystroglycan and study a type of mouse which has been genetically engineered to produce only the unmodified version of the protein to see what effects this has on hearing. In particular, Adam will focus on how the modified protein affects the development and maintenance of hair cells and the connections between hair cells and the auditory nerve. He will also study whether the complex is important in maintaining the high levels of potassium in the fluid surrounding the hair cells which are essential for the hair cells to signal to the brain.
Results from this project will give us a better understanding of the role of beta-dystroglycan in hearing. It is likely to be involved in both age-related and noise-induced hearing loss, so a better understanding could, ultimately, lead to new treatments to prevent hearing loss.