A mutation in the otoferlin gene causes inherited hearing impairment. The otoferlin gene codes for the massive otoferlin protein, which is in the part of the inner ear called the cochlea. Otoferlin is responsible encoding the sound and proposed to act as a calcium sensor for neurotransmission in inner hair cells of the cochlea. Murugesh Padmanarayana, PhD student in Biochemistry and Biophysics here at OSU, has been working on functional characterization of this protein in order to understand how it works and what it does to encode sound faithfully.
Why is it important to know the function of a protein and the functions of all of its parts? Different parts of proteins perform different tasks, and otoferlin’s most important parts are called C2 domains that bind calcium, lipids and other proteins. If there is a mutation in the otoferlin gene that affects the C2 domains, it abolishes neurotransmitter release and no sound will be detected. Murugesh has discovered that it is possible that only two functioning C2 domains are enough to rescue hearing. This is ground breaking because if only two parts are really necessary for hearing than proteins that look and act like otoferlin but are smaller may be able to restore hearing function to a person with inherited hearing impairment. Otoferlin at its complete size with six C2 domains is far too big to be administered through gene therapy. Murugesh hopes that his research may lead to further development of this protein as a potential treatment for inherited hearing impairment.
Murugesh came from a small village called Bagoor in India. There he is one of the few people to have attempted to or succeeded at obtaining a graduate degree, but Murugesh was a good student and he pushed himself to go farther. He graduated with a bachelor’s in Pharmacy from Rajiv Gandhi University of Health Sciences in India. After college, Murugesh worked at a pharmaceutical company for two years where he decided to pursue a career in medicinal chemistry. Murugesh left India and earned a master’s in Drug Design and Biomedical Science from Edinburgh Napier University in the United Kingdom where he was first involved in research. After working for two years in the protein science department of Agilent Technologies, he decided he wanted to return to graduate school for a PhD.
Murugesh contacted professors from 15 schools, based on their positive reply he applied to 7 schools, and we are fortunate that he chose Oregon State University and the Biochemistry and Biophysics Department where he works with Dr. Colin Johnson. Murugesh will continue working in protein biochemistry or protein engineering after his time here at OSU.
We are so thrilled to have Murugesh on the show this weekend, and we are excited to talk to him about his research with protein otoferlin. Be sure to listen to KBVR Corvallis 88.7 FM at 7 pm on Sunday, August 21 to hear from Murugesh, or stream the show live.