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When Teresa Nicolson brings middle-school girls into her laboratory and zebrafish facility at the Vollum Institute of Oregon Health & Science University, she's much more than a tour guide. She's a role model. An active member of Advocates for Women in Science, Engineering and Mathematics, Nicolson is a living example of what women can accomplish in biomedical research.
Leaders in her field of vertebrate mechanosensation—the way mechanical stimuli are converted into electrical nerve impulses and relayed to the brain—credit her with two groundbreaking discoveries: the identification of Trpn1 as a channel required for hearing in zebrafish, and cadherin 23 as a cell-adhesion protein found in the tip link of zebrafish hair cells. These two proteins play a key role in transduction of sound waves into electrical impulses in the fish ear.
Unlike other senses such as vision and smell, the molecular basis of hearing is poorly understood. Nicolson uses genetic methods in zebrafish to gain insight into the molecular basis of mechanotransduction—the conversion of mechanical energy into electrical signals. Using large-scale mutagenesis screens, she has identified 24 genes required for hearing and balance in the fishes' larval stage, and has cloned five zebrafish genes that are selectively expressed in hair cells. She gave the genes names that ring of space exploration (sputnik, mercury, skylab) because the mutant fish behave like space travelers in zero gravity, unable to orient themselves or navigate normally. The same genes are responsible for deafness in humans and mice.
The zebrafish mutant she characterized and called sputnik has similarities to the defects seen in a human deafness-blindness syndrome known as Usher's syndrome. Nicolson recently determined that the sputnik gene encodes cadherin 23 and showed it likely plays a direct role in mechanotransduction. The sputnik mutants are missing a part of the hair cell called the tip link that is postulated to physically tug open the transduction channels.
A second gene, which Nicolson named starmaker, determines the size and formation of calcium carbonate crystals in the "ear stones," which are important for the zebrafishs perception of gravity and sound. Human ears contain similar calcium carbonate crystals, called "ear dust," which are also important for balance and hearing.
Nicolson is beginning work to image the location of fluorescently tagged proteins and neuronal responses in hair cells in live transgenic zebrafish. Such experiments are only possible in the transparent zebrafish, where two hair cell populations can be imaged using conventional light microscopy. One set of hair cells is located right at the surface of the skin, making treatment with drugs and manipulations easy. Another population is located within the transparent ear.
Dr. Nicolson is also Associate Professor at Oregon Hearing Research Center, with a joint appointment at the Vollum Institute of the Oregon Health & Science University.
RESEARCH ABSTRACT SUMMARY:
Teresa Nicolson is interested in the molecular mechanisms underlying hearing and is using zebrafish genetics to identify key components for transduction and transmission in sensory hair cells.
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Photo: Derik Landry
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