Joseph Santos-Sacchi
Yale University, CT·Biophysics
Mammals hear quiet sounds and fine differences in pitch because the inner ear actively boosts incoming vibrations. This boost is called cochlear amplification.
- Fields
Biophysics
Neuroscience
Physiology
- Topics
prestin
outer hair cells
cochlear amplification
- Grants
- 1 known grant, through May 2027
What they work on
- Determine the cryo-EM structure of prestin, the outer hair cell motor protein behind cochlear amplification, in the expanded state that voltage brings about, complementing the known contracted-state structure.
- Use temperature changes and prestin mutations that shift its voltage sensitivity to trap and identify the different shapes the protein takes during normal outer hair cell activity.
- Apply recent cryo-EM image-processing advances to resolve distinct prestin conformations within the protein samples.
- Model prestin's structural changes under voltage control with molecular dynamics simulations, which follow atomic motion over time.
More about the research
It depends on outer hair cells (OHCs), sensory cells in the cochlea that change length when the voltage across their membrane changes. That shape change is driven by prestin, a motor protein packed into the cells' side walls. Knowing how one molecule can power this amplifier is key to understanding normal hearing and why it fails when outer hair cells are damaged.
Why it matters
Damage to outer hair cells is behind hearing problems that affect millions of people. Defining how prestin changes shape under voltage may clarify how these cells give mammals such sensitive hearing. Over time, this structural knowledge could inform ways to combat outer hair cell disorders and the hearing loss that results from them.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jong-Hoon Nam
University of Rochester, NY·Biomedical Engineering
Measure how length changes in outer hair cells deflect the stereocilia, the hair-like sensors on hair cells, using in vitro cochlear preparations where individual outer hair cells are controlled electrically, chemically and mechanically.
Su-Hua Sha
Medical University of South Carolina, SC·Neuroscience
Test whether prolonged activation of AMPKα, an energy-sensing enzyme, by CaMKK2, LKB1 or reactive oxygen species triggers outer hair cell death after noise exposure in adult mice, using virus-delivered shRNA to silence these genes.
Karl Grosh
University of Michigan, MI·Biomedical Engineering
Design and fabricate a multi-resonant piezoelectric MEMS accelerometer co-designed with an application-specific integrated circuit, and reach a 5-milligram packaged implantable sound sensor using flip-chip packaging that eliminates printed circuit board mounting.
The school
Yale University: 73 labs on PI Pages, $1.5B a year on research, 438 research doctorates a year.
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