Project Grant F32DC022491
- This federal Project Grant award of $265,410 from the National Institute on Deafness and Other Communication Disorders (NIDCD) under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) supports research to characterize how heterogeneous regional expression of mechanoelectrical transduction (MET) channel components contributes to vestibular hair cell function and development, and whether early MET expression defines a critical period for gene replacement therapy....
- This three-year Project Grant from the National Science Foundation's Mathematical and Physical Sciences program, totaling $731,931, will fund research into the nonlinear dynamics of auditory hair cells and efferent neurons. Specifically, the University of California, Los Angeles will directly measure how stimulation of efferent neurons affects the sensitivity of hair cells to detect weak signals and withstand strong stimuli. Researchers will compare experimental findings to nonlinear dynamics...
- This Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the federal grant program "Research Related to Deafness and Communication Disorders" (CFDA 93.173), supports research into how phospholipid homeostasis regulates the function and health of sensory hair cells in the inner ear. The $115,707 award, with a period of performance from September 30, 2025 to April 30, 2029, will investigate the role of the phospholipid flippase...
- This Project Grant award of $637,500.00 was provided by the National Institute on Deafness and Other Communication Disorders (NIDCD) under the federal Research Related to Deafness and Communication Disorders program (CFDA 93.173). The goal of the project is to understand the forward transduction that drives inner and outer hair cell stereocilia, as well as the reverse transduction that amplifies motion in the human cochlea, using a novel finite element modeling technique. The research will focus...
- This federal Project Grant award of $448,687, provided by the National Institute on Deafness and Other Communication Disorders (NIDCD) under the Research Related to Deafness and Communication Disorders program (CFDA 93.173), supports research to investigate the role of calcium regulation in outer hair cells (OHCs) and their sensitivity to cochlear injury. The research aims to enhance understanding of the mechanisms that protect OHCs, which act as sentinels of cochlear injury, from damage due...
- This five-year, $734,582 Project Grant from the National Institute on Deafness and Other Communication Disorders will fund research at Lehigh University to investigate the developmental determination of central auditory physiology by the inner ear. The grant is part of the Research Related to Deafness and Communication Disorders program. Specifically, the university will develop a model of repatterned frequency representation in the chick inner ear by overexpressing the bone morphogenetic...
- This Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the Research Related to Deafness and Communication Disorders (CFDA 93.173) program, will fund the development of a CRISPR-based toolkit to investigate hair cell transcription factors in inner ear organoids. The $249,000 grant awarded to Merrimack College will enable the research team to: 1) Define the transcription factors involved in in vitro inner ear organoid hair cell development...
- This $1,145,674 federal Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health (NIH), will fund research at Case Western Reserve University to investigate the role of TMC proteins in hair cell mechanotransduction in zebrafish. Specifically, the project aims to determine if TMCs contribute differently to zebrafish hearing, the role of TMCs in hair cell mechanotransduction and lateral line-mediated...
- This Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the CFDA program "Research Related to Deafness and Communication Disorders" (93.173), provides $693,856 to The Regents of the University of California, San Francisco (UCSF) to conduct research on the structure and function of coordinated neural activity in the auditory system. The key objectives of this 5-year research project are to: 1) Identify coordinated neural...
- This Project Grant award of $670,318, provided by the National Institute on Deafness and Other Communication Disorders (NIDCD) under CFDA 93.173 - Research Related to Deafness and Communication Disorders, will fund research to investigate the biological functions of the CHD7 gene and its role in the inner ear development pathology of CHARGE syndrome. The key objectives are to: 1) Establish human embryonic stem cell lines with specific CHD7 mutations to study their impact on gene/protein...
INVESTIGATING THE ROLE OF TIP LINK BIOPHYSICS ON MET FUNCTION - PROJECT SUMMARY: BROAD IMPACT: HAIR CELLS (HCS) ARE THE SENSORY TRANSDUCTION CELLS OF THE AUDITORY AND VESTIBULAR SYSTEMS. WHEN A MECHANICAL STIMULUS SUCH AS SOUND OR LINEAR, GRAVITATIONAL, OR ANGULAR ACCELERATIONS ARE APPLIED TO THESE HAIR CELLS, SMALL MICROVILLUS-LIKE, ACTIN-FILLED PROTRUSIONS CALLED STEREOCILIA FROM THE APICAL POLE OF THE HCS ARE DEFLECTED. THIS CAUSES FILAMENTOUS TIP LINK PROTEIN COMPLEXES AT THE TIPS OF HAIR CELL CALLED STEREOCILIA TO PULL UPON AND LEAD TO THE OPENING OF MECHANOELECTRICAL TRANSDUCTION (MET) CHANNEL COMPLEX. THE OPENING OF MET CHANNELS CAUSES AN INFLUX OF POSITIVELY CHARGED IONS THAT DEPOLARIZE THE HCS, RESULTING IN A VARIETY OF PHYSIOLOGICAL PROCESSES FROM SYNAPTIC TRANSMISSION TO NERVE FIBERS TO PHYSICAL CHANGES IN HC LENGTH BY A PHENOMENON KNOWN AS ELECTROMOTILITY. HOWEVER, THERE IS A REIGNING QUESTION OF THE ROLES OF THE PROTEIN CONSTITUENT OF THE TIP LINKS AND THE MET CHANNEL COMPLEX IS UNCLEAR. FOR EXAMPLE, WHETHER TIP LINKS MODULATE THE MECHANICAL STIMULI IN HCS BY ACTING AS DAMPERS, EXTRA MASSES, OR SPRINGS IS YET TO BE DISCOVERED. THESE TIP LINKS ARE COMPOSED OF FOUR LARGE EXTRACELLULAR PEPTIDE CHAINS - TWO OF PROTOCADHERIN 15 (PCDH15) AND TWO OF CADHERIN 23 (CDH23). DUE TO LIMITATIONS IN HETEROLOGOUS EXPRESSION OF MET CHANNEL COMPLEX PROTEINS, MET MUST BE STUDIED IN ANIMAL MODELS. RECENT GENE THERAPY DEVELOPMENTS PROVIDE A GREAT TOOL TO STUDY ONE COMPONENT OF TIP LINKS: PCDH15. HERE, THIS PROJECT SEEKS TO EXPLOIT THIS NOVEL PROTEIN MANIPULATION TECHNIQUE TO STUDY THE BIOPHYSICAL PROPERTIES OF TIP LINKS AND THE INFLUENCE OF THESE PROPERTIES ON THE MET CHANNEL FUNCTION. AIM 1: TO UNCOVER WHETHER THE LENGTH OF THE TIP LINKS IS IMPORTANT FOR MET, MET FUNCTION OF MINIATURIZED PCDH15S WITH SHORTENED LENGTHS WILL BE COMPARED TO THAT OF WILD-TYPE- LIKE TIP LINKS. AIM 2: TO REVEAL THE ROLE OF CA2+-BINDING SITE-MEDIATED FLEXIBILITY ON THE HAIR-CELL MET FUNCTION, TIP LINKS FORMED BY MUTANT PCDH15S WILL BE COMPARED AGAINST WILD-TYPE-LIKE TIP LINKS USING SINGLE-CELL ELECTROPHYSIOLOGY. AIM 2.1: COMPUTATIONAL SIMULATIONS THAT ARE USED TO PREDICT PROTEIN DYNAMICS WILL BE USED TO ESTIMATE THE FLEXIBILITY OF THE TIP LINKS WHEN SPECIFIC CA2+ BINDING SITES ARE PERTURBED. AIM 2.2: MET CURRENTS OF DIFFERENT CA2+-BINDING-SITE-PERTURBED MUTANT PCDH15S WILL BE MEASURED TO REVEAL THE EFFECT OF CA2+-BINDING AT SPECIFIC SITES ON MET. TRAINING: THIS PROJECT AIMS TO FORGE THE APPLICANT INTO WELL-ROUNDED AUDITORY NEUROSCIENTIST. IN PURSUIT OF THIS GOAL, THE PROJECT WILL TEACH THE APPLICANT INNER EAR WHOLE-CELL HAIR-CELL ELECTROPHYSIOLOGY, STEREOCILIA BUNDLE DEFLECTION, CONFOCAL MICROSCOPY IMAGING, ANIMAL HANDLING, AND IN SILICO METHODS. ADDITIONAL TRAINING WILL PROVIDE DEDICATED TIME TO ALLOW THE APPLICANT TO GROW HIS NETWORK WITH COLLABORATIONS ACROSS MANY DIFFERENT LABORATORIES. TOGETHER, THIS PROJECT SEEKS NOT ONLY TO DEVELOP A STRONG SCIENTIST, BUT ALSO TO INCREASE OUR COLLECTIVE KNOWLEDGE ON THE BIOPHYSICS UNDERLYING THE HAIR-CELL MECHANOTRANSDUCTION FUNCTION.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $75.5k | 7/15/25 | ||
| Not listed | $0 | 8/28/24 | ||
| Not listed | $73.8k | 8/28/24 |