Abstract
This project will identify previously unknown proteins in auditory hair cells and characterize their function. The outcomes will provide useful knowledge for the development of therapeutic approaches for hearing impairment. The auditory hair cells are found in the organ of Corti (in the inner ear). These cells are specialized sensory cells that transduce auditory signals into an electrical signal that is sent to the brain. Some of the proteins involved in auditory hair cell functioning are already identified by classical genetic approaches - via identification of causative genes in patients with hearing impairment or via mouse models. However, the majority of proteins involved in critical complexes for hearing remains unidentified. This project will identify new components of the lower tip-link complex in the organ of Corti with affinity purification (AP) followed by mass spectrometry (MS). The latest evolutions in proteomic techniques resulting in a gain in MS sensitivity now make this possible for the first time. Our preliminary data confirms the feasibility of this AP-MS approach for the hair cell complexes. New components will be identified and for a selection of these the molecular interactions with other proteins of the complex will be analysed in-depth. Additionally, we will identify the location of these proteins in the hair cells and their effect of ablation on hearing.
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