Research

Goals

Hair cell DEAFNESS genes studied by the Nicolson Lab:

MECHANOTRANSDUCTION
cdh23, ush1c, pcdh15a, myo7aa, myo6b, IhfpI5a, tmie, ap1b1, tomt, tmc1/2a/2b

SYNAPTIC TRANSMISSION
cav1.3a, vglut3, synj1, rbc3a, nsfa, nav1.6a

The goals of the Nicolson lab are to understand the molecular basis of the senses of hearing and balance. Many of the genes that we have identified in behavioral screens for auditory/vestibular deficits are implicated in human hearing loss.

Picture: Image of live hair cells within the inner ear of an undissected larval fish. Hair bundles are expressing a red fluorescent protein (actin), whereas the kinocilia and cell bodies are expressing a yellow fluorescent protein (tubulin).

Methods

We use zebrafish to explore the basic biology of the auditory/vestibular system in vertebrates and to provide

animal models of human hearing loss.

Our methods include:

  • forward and reverse genetics
  • live-cell imaging of whole animals
  • cellular and behavioral analyses
  • transcriptomics

Sensory hair cells of the inner ear and lateral line organ in larvae (k, kinocilium; hb, hair bundle; hc, hair cell body; sc, supporting cell; 5 dpf, 5 days postfertilization).

Using transgenic fish to image dopaminergic efferents (green) innervating a neuromast (hair cells in magenta).

Rotation of the fish excites the utricle of the inner ear leading to reflexive eye movements.

Mechanotransduction in Hair Cells

We are interested in how hair cells transduce mechanical stimuli into electrical signals. To date, we have identified more than nine genes that are specifically required for mechanotransduction, including components of the transduction machinery. Our goal is to understand the precise role of these components in this fascinating process.

Synaptic Transmission in Hair Cells

Hair cells communicate to neurons using ribbon synapses. How this communication is achieved at the molecular level and how these synapses develop are some fundamental questions that we are addressing using a wide range of methods.

Beyond the First Synapse

We have begun to characterize a rarer class of mutants that have defects that are downstream of hair cells and appear to affect more central processing of auditory and vestibular stimuli.

Stay tuned!