The mammalian cochlea (inner ear) is an extremely complex and organised structure, made up of many different types of cells, which all work together to detect sounds and pass this information onto the brain for decoding. Some of the most important cells in the cochlea are the sensory hair cells, the cells that detect and convert sound vibrations into electrical impulses that are then passed onto the brain (via the auditory nerve).
Although we have a good understanding of how hair cells work, we still don’t know a great deal at the molecular level about how they develop into cells capable of detecting sound vibrations. Uncovering and understanding the genes and processes involved in establishing and maintaining hearing is critical if we hope to understand the processes that lead to hearing loss.
Cell adhesion molecules are proteins found on the surface of cells that form bonds with adjacent cells or structures, acting like a ‘molecular glue’ that holds cells together. There is a group of cell adhesion molecules, called the Basigin family, which has three members, called Basigin, Neuroplastin and Embigin. All three proteins have been shown to be important for the correct development of nerve cells. There is also evidence suggesting that Neuroplastin and Embigin are important for correct development of the cochlea – mice which lack these proteins develop hearing loss. It is likely, then, that these proteins are needed for correct hair cell function.
The researchers will study mice which have been genetically engineered to lack these three proteins, to determine how each of them is needed for hearing. They will particularly focus on how these proteins affect the correct formation and maintenance of the connections (synapses) between hair cells and auditory nerve cells. These synapses are needed for hair cells to pass on signals about sound to nerve cells. This project will therefore help to determine the role of these proteins in transmission of signals to the brain (called neurotransmission) by hair cells.
Current treatments for hearing loss are limited to hearing aids, which amplify sound, or cochlear implants, which directly stimulate the auditory nerve. These devices bring benefit to many, but do not restore natural hearing. More recently, gene- and stem cell-based therapies have been investigated as possible ways to restore hearing. However, these approaches ultimately rely on knowing about the genes and biological processes involved in hearing. The results of this project will add to this knowledge by increasing our general understanding of hair cell neurotransmission, which is required for hearing.