The role of membrane bilayer composition on mammalian mechanoelectrical transduction and adaptation in the inner ear

• Applicant: Thomas Effertz, Ph.D.
• Subject Area: Otolaryngology, Phoniatrics and Audiology ; Sensory and Behavioural Biology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 263028567

Impairment of hearing is the most prevalent sensory deficiency found in humans. About 360 million people, about 5% of the world population, suffer from disabling hearing loss, and another 300 million have different levels of hearing loss. Understanding how the reception and perception of sound works is thus an important subject. Hearing relies on the direct mechanical opening of mechano-electrical-transduction channels (MET-channels). How those MET-channels translate force into electrical signals, however, remains largely unknown. Also the molecular identity of the channel itself is unknown, even after three decades of intensive search. What we do know, though, is that age related and noise induced hearing loss both target the mechano-electrical-transduction machinery. Understanding how that machinery operates and which factors make it more resilient/sensitive to damaging influences is thus of high importance. At this point we know little about the inner workings, for example the force relay to the channel, and previously well understood processes (based on lower vertebrate data) turned out to be not transferable from lower vertebrates to mammals. For example our lab was recently able to show that different to the adaptation process (which is important for sensitive hearing) in lower vertebrate, adaptation in mammals is not driven by Ca2+. This made us rethink other processes as well, where the understanding is also mostly based on non-mammalian data. One such process is the force relay through a chain of proteins to the mechano-electrical-transduction channel. Our hypothesis is that the mammalian auditory MET-channel, just as other MET-channels, is affected by changes in its lipid surroundings, which could affect channel gating or adaptation. Thinking further, it might be that the mechanicals properties of the membrane (viscosity, stiffness etc.) could be employed as mechanical filters for the MET-channel and thus be part of the underlying process for our sensitive hearing. On the experimental side we will increase/decrease the concentration of defined lipid species in the cell membrane of auditory hair cells and investigate the effect on MET-currents. We will also test cholesterol, drugs, and toxins, which have been shown to affect other MET-channels. Our goal at the end of our proposed research will be to have identified essential lipid species for MET-channel function and solved the possible involvement of the lipid in adaptation and force relay functions. This might open up new avenues of treatment or protective measures, as alterations of the bilayer could render the MET-machinery more resilient to noise damage.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Anthony Ricci, Ph.D.