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The long and winding route of sound

Researchers examined DNA samples of 1,200 deaf Israeli-Jews, in order to understand the damage caused to the structure of the proteins in the hearing system

Immunofluorescence of the mouse inner ear. The spiral structure of the inner ear consists of hair cells and supporting cells, which together allow us to hear. Each cell type is shown in a different color. Image: Dr. Shahar Tiber
Immunofluorescence of the mouse inner ear. The spiral structure of the inner ear consists of hair cells and supporting cells, which together allow us to hear. Each cell type is shown in a different color. Image: Dr. Shahar Tiber

Hearing impairment (deafness) is an impairment of the normal functioning of the auditory system, in one area or in several locations along the auditory pathway. The causes can be genetic or acquired (physical injuries such as noise trauma). This is the most common sensory impairment, which affects many areas of life (such as studies, employment and financial situation), from which more than five million people in the world suffer.

Prof. Keren Avraham, from the Department of Human Molecular Genetics and Biochemistry, and Dean of the Faculty of Medicine at Tel Aviv University (the first woman to hold this position), together with her team, researches genetic diseases and focuses on deafness in Jewish Israelis (of any origin). According to her, "many populations in Israel suffer from hereditary dementia. We are often the first to discover the genetic changes that cause deafness in Israelis. When we published them in the past, researchers from other countries tested them in additional populations and found similar changes, in the same genes."

There is a direct connection between the research of Prof. Avraham and her team and the clinic - the information about the genetic changes they discover is transmitted to the Ministry of Health, hospitals and doctors, is given to the relevant families and can help them in family planning and preventing the transmission of the mutations from generation to generation. At the same time, this information is the basis for research being carried out in Prof. Avraham's laboratory aimed at gene therapy (insertion of a normal gene into cells or tissues affected by a mutation) or cell therapy (injection of cells or tissue in their intact form to replace those damaged). Immunofluorescence of the mouse inner ear. The spiral structure of the inner ear consists of hair cells and supporting cells, which together allow us to hear. Each cell type is shown in a different color. Image: Dr. Shahar Tiber

"The changes in the genes impair the production of proteins related to the audio system, and we are investigating the mechanisms responsible for this (among other things using the genetic editing technology CRISPR). After that, we produce mouse models with deafness similar to that of humans and try to correct it through gene or cell therapy and restore their hearing," explains Prof. Avraham.

The latest research by Prof. Avraham and her team, which won a grant from the National Science Foundation, was done in collaboration with the Kahn-Segol-Maccabi Institute for Research and Innovation established by the Maccabi Health Services Hospital Fund. It involved deep genetic sequencing of DNA samples taken in a blood test from 1,200 deaf Jewish Israelis. Some were born this way and for some the deafness developed over time (the hypothesis is that for 50%-60% the cause is hereditary). Genetic changes that lead to deafness were found in 38 genes, 22 of which were discovered for the first time as being involved in deafness (and they are still not recognized as such in the world of research).

To show that the same genetic changes that were found actually cause deafness, the researchers modeled the structure of the proteins that went wrong in the pens and compared them to the normal structure of those proteins. To this end, they developed a computer program, in which they assimilated the data of the genetic changes and thus examined the XNUMXD structure of the damaged proteins in comparison to the XNUMXD structure of the normal proteins (the proteins consist of chains of hundreds of amino acids and in order for them to function these chains have to fold into a precise XNUMXD structure ). The analysis of the data obtained from the software is still ongoing and in the future the researchers hope that it will be possible to focus on healing the damage caused to each specific structure.

Hundreds of genes are involved in deafness, but what is interesting is that each gene has a different role in the hearing system, and it contributes to the production of different proteins. Therefore there is a huge variety of genetic changes that lead to deafness.

"Hundreds of genes are involved in deafness, but what's interesting is that each gene has a different role in the hearing system (for example, responsible for different types of cells in the inner ear), and it contributes to the production of different proteins. Therefore, there is a huge variety of genetic changes that lead to deafness, and our task is to understand how each of them causes hearing damage. We now have work for years," Prof. Avraham concludes.

Life itself:

The Abraham Foundation

Prof. Keren Avraham, married + child, lives in Ramat Aviv. Born in Canada and raised in the USA and immigrated to Israel 32 years ago. She holds a BA in Biology from Washington University in St. Louis, Missouri, USA, a PhD from the Weizmann Institute of Science and a post-doctorate from the National Cancer Institute in Maryland, USA. She won awards for her scientific achievements. She recently received an award from the Ilanit conference (31 Israeli associations for experimental biology) - for outstanding scientific work and leadership. She really enjoys tutoring students ("that's what attracts me to science") and in her free time likes to swim.