This is a PhD studentship being carried out by Rafael Kochaj in the laboratory of Professor Karen Steel at King’s College London. Rafael began work on this project in October 2015. He'll finish in September 2018.
Progressive, high-frequency hearing loss is a common form of hearing loss that occurs slowly over time (as you age). It happens when the special sensory hair cells in the inner ear (cochlea) are lost or damaged. High-frequency (high-pitched) sounds are perceived at the bottom of the cochlea and low-frequency (low-pitched) sounds at the top.
Peroxisomes are small bodies inside the cells that play an important role in various chemical reactions, including breaking down lipids (fats, oils etc.) and processing waste materials. They are important for maintaining the normal functioning of a cell – their numbers can increase or decrease, depending on the stresses to which a cell is exposed. Mutations in genes that are involved in peroxisome formation or function result in a variety of different, often severe, disorders.
Pex genes make proteins that are involved in peroxisome formation and division (to increase the number of peroxisomes when needed). Pex3 is a particular Pex gene required for this process. When scientists analysed a mouse in which Pex3 was mutated, they found it had a number of defects, including high-frequency hearing loss.
The aim of Rafael's project is to understand the role of peroxisome defects in hearing loss. He's analysing a mouse with a Pex3 gene mutation as a model of human hearing loss, to understand the processes involved in causing the hearing loss, specifically the effects on peroxisomes and lipids. He wants to find out if hearing loss in these mice is progressive, what the underlying cellular processes involved are, and where in the auditory system the damage is occurring.
We believe that Rafael's research will improve our understanding of the causes of progressive, high-frequency hearing loss. We hope it will lead to the identification of molecular processes that can be targeted with drugs to prevent this common form of hearing loss.