Turning on Cell Fate Switches to Regenerate Mammalian Inner ear Hair cells

Work done in the lab of Prof.Andrew K. Groves at Baylor College of Medicine, Houston, TX.

About author

Amrita is a Science writer and Geneticist currently working at Tempus labs in Chicago. She enjoys sharing her enthusiasm for science with large audiences through multiple modes like blogs, talks, posters, and videos. She often expresses her creativity through colourful scientific illustrations and sketches to describe key scientific messages. Before venturing into scientific communications full time, she trained as a bench scientist for 9 years. She got her Ph.D. in Genetics and Genomics from the Baylor College of Medicine in Houston, Texas where she worked on hair cell reprogramming in the mouse inner ear. Prior to that, she got her master’s (by research) in Biological Sciences from the Department of Biotechnology, IIT Madras. Her project was on studying the association between candidate gene polymorphisms and hypertension in the Indian population. In her spare time, Amrita enjoys anything and everything around cooking, music and gardening!

Interview

How would you explain your research outcomes to the non-scientific community?

Not many people know that Beethoven was profoundly hearing impaired when he composed the best of his symphonies. Currently, about 48 million Americans suffer from hearing loss making it the third most common public health issue in the United States. Hair cells in the inner ear are specialized cells possessing ‘hairs’ or stereocilia which convert sound stimuli into electrical impulses. Hearing loss occurs when these hair cells fail to regenerate in the event of death or damage. The risk factors for hearing loss include age (most common), some antibiotics and chemotherapy drugs, and occupational/recreational noise. None of the current therapies for hearing loss can regenerate hair cells. The 1980s gave rise to a wave of enthusiasm in looking at the prospect of hair cell regeneration to restore hearing. Several labs independently discovered that birds could regenerate their hair cells within three weeks after deafening. Further studies concluded that regeneration occurred in non-mammalian vertebrates naturally but not in mammals.

Hair cell reprogramming is a potential regeneration strategy involving the overexpression of certain key proteins (namely transcription factors) in unique combinations. Based on previous studies, we chose three such hair cell specific transcription factors namely ATOH1, GFI1 and POU4F3. We compared the reprogramming efficiency of overexpressing transcription factor ATOH1 alone, combinations of GFI1, ATOH1 and GFI1, ATOH1, POU4F3 in the mouse inner ear specifically in non-sensory cells. This was done at two timepoints (neonatal study between 1 and 8 days of age) and postnatal (study between 8 and 15 days of age). We found that in the neonatal stage, the inner ears of mice respond equally well to all three combinations and showed enhanced hair cell regeneration from non-sensory cells. However, in the postnatal stage, the three-factor combination led to better regeneration features (both at morphological and at a cellular/transcriptomic level) as compared to the others tested.

We believe that these results will help in better understanding the roadblocks of mammalian hair cell regeneration. It will also help in designing effective gene therapy strategies for restoring human hearing in future. After all, hearing is an integral part of an enriched quality of life.

How do these findings contribute to your research area?

These findings are key to advancing our existing understanding of the mammalian inner ear hair cell regeneration process. From a therapeutic standpoint, transcription factor-mediated reprogramming and the underlying biology associated with its function shall enable fine-tuning of current gene therapy approaches for long-term hearing loss treatment.

“Our findings are key to advancing our existing understanding of the mammalian inner ear hair cell regeneration process”

What was the exciting moment during your research?

I can recall several exciting moments during my research. Most of these moments were centred around finding something unexpected and brainstorming with my colleagues to identify what could be the contributor (sometimes it was simply a human error in the experiment, some other times it was genuinely an interesting find with a scientific basis to it). Sitting in front of the confocal microscope and looking at the images it captured is by far the best feeling!

What do you hope to do next?

In terms of this study, future work will be necessary to determine whether more functional hair cells can be generated with additional hair cell-specific transcription factors. We emphasize that our present work focuses exclusively on the intact mouse inner ear. Studying aspects of regeneration with respect to other parts of the hearing architecture including the associated membranes, ionic balance, sensory neurons etc are important and critical for advancing towards converting this into a potential therapeutic option.

In terms of my life, I have already moved on to pursue my passion for scientific communications in the biotech industry. I currently work in the precision medicine space and am a science writer.

Where do you seek scientific inspiration from?

Nature! The world around us is beautiful and there is so much to uncover and learn about. The human body in itself is fascinating and nuanced to a point where I feel a lifetime isn’t enough to know everything it holds.

How do you intend to help Indian science improve?

I strongly believe that there is a need for better communication of scientific findings more than ever. The fact that everyone deserves to share and enjoy science is what continues to motivate me. However, as science gets complex, communicating it to a non-expert audience gets equally complex. I believe it is important for every scientist to equip themselves with a well-defined science communication skill set. This will enable them to get across their science to any kind of audience without ‘dumbing’ it down. A lot of good science and hard work is lost behind bad, boring presentations even today. I would like to contribute in the niche area of bridging the gap between scientists and scientifically enthusiastic audiences in India by providing training towards acquiring the right skill sets for enabling the same.

Reference

Amrita A Iyer et al., Cellular reprogramming with ATOH1, GFI1, and POU4F3 implicate epigenetic changes and cell-cell signalling as obstacles to hair cell regeneration in mature mammals. eLife. https://elifesciences.org/articles/79712

Copy Editor

Ritvi Shah

Postgraduate at Vikram Sarabhai Institute

Postgraduate at Vikram Sarabhai Institute of Cell and Molecular Biology, Gujarat. She is a neuroscience enthusiast. Apart from that, she enjoys reading and trying her hand at sciart.

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