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      The ON and OFF switches of hearing genes

      A team of researchers, led by Professor Karen Avraham at Tel Aviv University in Israel, has analysed the processes underlying how genes are turned ON and OFF during the formation of the inner ear. Carina Santos, from our Biomedical Research team, tells us more about their work and why it’s so important.

      By: Carina Santos | 17 January 2019

      The cochlea is the organ responsible for our sense of hearing. It is located in the inner ear, and contains cells called ‘hair cells’ and ‘supporting cells’. Hair cells work as interpreters between our ears and brain, detecting mechanical sound waves and translating them into electrical signals that are sent to the brain. Supporting cells maintain a healthy and structured environment in the cochlea that is needed for the hair cells to work properly. Defects in the structure or function of the cochlea lead to hearing problems.

       

      A blueprint for the cochlea

      Our genes contain the information that determine most of our characteristics, including those of the cells in the cochlea.  More than 100 genes have so far been linked to hearing and changes (mutations) in those genes can lead to hearing loss and/or deafness. Although we know a lot about the genetics of hearing loss, this is not the case when it comes to the mechanisms that turn these hearing genes on or off. One of these mechanisms is a process called ‘epigenetics’. Epigenetic processes don’t change the genes themselves, but instead they control whether genes are activated or inactivated. Epigenetics allows the body to ensure that the right genes are switched on or off at the right times in the cochlea to correctly produce working hair cells and supporting cells when the inner ear is forming, so that we are born with healthy hearing.

       

      On-off switch – ‘Epigenetics is the way in which the body controls how genes are switched on or off. This ensures that different parts of the body develop and work correctly’.

      These epigenetic processes are also the reason why many of the genes that could regenerate hair cells are kept switched off. This is why hearing loss in people is permanent – once these cells are damaged and die, they can’t be regrown. Up until now, we didn’t know very much about these on and off epigenetic switches in the cochlea, but a recent study that we helped to fund, published last November in the scientific journal Scientific Reports, has revealed more about these switches and the hearing genes they control.

      Learning more about inner ear epigenetics

      Professor Avraham’s team, at the University of Tel Aviv, working with researchers from the USA and Italy, studied the activity of these epigenetic switches in the inner ear of mice, during the formation of the cochlea. This allowed them to identify which genes were switched on and off in the inner ear, and when, as the cochlea formed. Using cutting edge technology, the researchers were able to study all the genes in the inner ear of these mice at the same time, looking at a particular chemical modification of the genes (called ‘methylation’), which we know is one of the epigenetic switches used to turn genes off. Their work identified several new genes that are controlled by these epigenetic switches in the inner ear that are crucial for the correct development of the cochlea and of hearing itself.

       

      DNA methylation - ‘One of the ways in which genes can be switched off is through a chemical modification of the DNA sequence called methylation, as illustrated in this image. (Christoph Bock, Max Planck Institute for Informatics [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)], from Wikimedia Commons)’

       

      Why is this work important?

      We are born with a defined number of hair cells in the cochlea, and we lose these during our lifetime, perhaps because of exposure to loud noise, through having to take certain life-saving drugs that damage hair cells as a side-effect, because of genetic mutations, or simply with age. Unfortunately, we cannot regenerate these hair cells, in part because of the epigenetic switches that keep certain genes turned off. Professor Avraham’s work is therefore of great importance, as it allows us to better understand how these epigenetic switches work and which hearing genes they control. This knowledge is crucial to be able to develop medicines that can change the function of these switches, so that the genes needed to regenerate hair cells are switched back on to restore hearing.

       

      We funded a pilot study of this work through our Flexi Grant scheme, which enabled the researchers to gather data to apply for a much larger grant to continue and complete the work that they have now published. This is a great example of how our funding can kick-start larger research programmes that bring important knowledge to the research field and contribute to speeding up the development of treatments for hearing loss.

       

      Find out more

       

      This work was published last year in the journal Scientific Reports – you can read the published paper on the journal website. (Full reference: Yizhar-Barnea et al, DNA methylation dynamics during embryonic development and postnatal maturation of the mouse auditory sensory epithelium, Scientific Reports (2018).)


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      You can find out more about the research we’re funding in our biomedical research section.


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