Teresa Nicolson Ph.D.
Professor, Oregon Hearing Research Center
Joint Appointment, Vollum Institute
Office: MRB 816B
After receiving her B.S. in Biochemistry at Western Washington University, Teresa Nicolson received her Ph.D. in Biological Chemistry in 1995 from the University of California, Los Angeles. She then trained as a post-doctoral fellow at the Max Planck Institute for Developmental Biology in Tuebingen, Germany. In 1999, Teresa became an independent Group Leader at the same institute. In 2003, she was appointed as an assistant professor to the Oregon Hearing Research Center (OHRC) at OHSU with a joint appointment in the Vollum Institute. She was promoted to associate professor in 2005 and professor in 2014. Teresa was an HHMI Investigator from 2005 to 2013.
Summary of Current Research
The Nicolson lab studies the molecular basis of hearing and balance in zebrafish. In the inner ear or lateral line organ of the fish, sensory hair cells transduce mechanical energy into electrical signals. Depolarization leads to graded release of neurotransmitter at the basal end of hair cells. The lab is focused on identifying genes required for function of the transduction apparatus in the hair bundle and neurotransmission at the specialized ribbon synapses.
Past large-scale screens of over 7000 genomes have yielded two dozen genes that are specific to auditory/vestibular function in zebrafish larvae. Several of the genes including myosin VIIa, cadherin 23, and protocadherin 15a are important for hair-bundle integrity and function. Cadherin 23 and Protocadherin 15 are particularly interesting as weak alleles leave zebrafish hair bundles intact, yet receptor potentials are affected. Collective evidence presented by the Nicolson lab and other labs suggests that these novel cadherins form the extracellular filaments that mechanically gate transduction channels in hair cells. To identify how these cadherins are coupled to the transduction machinery, we used a membrane-based screen to find interacting partners of zebrafish Pcdh15a. This unbiased approach led to the identification of protein-protein interactions with the Transmembrane channel-like proteins Tmc1 and Tmc2a. Mutations in mammalian TMC1 are associated with deafness, and TMC1 and TMC2 are proposed to be subunits of the mechanotransduction channel in auditory/vestibular hair cells. Our work establishes a link between the Tmc subunits and a central component of the transduction apparatus, Pcdh15a (see Maeda et al., 2014).
Ongoing efforts of the Nicolson lab are largely directed at cloning the genes identified from the forward genetic screens and understanding the function of the proteins. In addition, new ways of analyzing the collection of auditory/vestibular mutants are being developed such as measuring the vestibulo-ocular reflex, and recording currents in post-synaptic neurons to assess synaptic transmission. Efforts are also directed at creating transgenic lines driving hair-cell specific expression of tagged proteins or calcium indicators for live imaging experiments.
By exploring the mutant phenotypes at the behavioral, cellular and electrophysiological level, we aim to gain a better understanding of the basic molecular mechanisms involved in transduction and transmission in hair cells, and to apply our findings to understanding the pathology of congenital deafness in humans.
Erickson T, Morgan CP, Olt J, Hardy K, Busch-Nentwich E, Maeda R, Clemens-Grisham R, Krey JF, Nechiporuk A, Barr-Gillespie PG, Marcotti W, Nicolson T. (2017) Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt). eLife 6 pii: e28474.
Maeda R, Pacentine IV, Erickson T, Nicolson T. (2017) Functional analysis of the transmembrane and cytoplasmic domains of Pcdh15a in zebrafish hair cells. J. Neuroscience 37:3231-3245.
Toro C, Trapani J, Pacentine I, Maeda R, Sheets L, Mo W, Nicolson T. (2015) Dopamine modulates the activity of sensory hair cells. J. Neuroscience 35:16494-16503. [Featured Article]
Erickson T, Nicolson T. (2015) Identification of sensory hair-cell transcripts by thiouracil-tagging in zebrafish. BMC Genomics 16:842.
Maeda R, Kindt KS, Mo M, Morgan CP, Erickson T, Zhao H, Clemens-Grisham R, Barr-Gillespie PG, Nicolson T. (2014) Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. Proc. Natl. Acad. Sci. 111:12907-12912.
Kindt K, Finch G, Nicolson T. (2012) Kinocilia mediate mechanosensitivity in developing zebrafish hair cells. Developmental Cell 23:329-341.