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HEARING AND BALANCE

 

Virginia Merrill Bloedel Hearing Research Center (VMBHRC)

About the Center

The Virginia Merrill Bloedel Hearing Research Center, adjacent to the hospital in a 14,000 square foot multi-story complex, was funded by the Bloedel family and dedicated to the study of hearing and hearing loss. It is jointly administered by the Department of Otolaryngology-Head and Neck Surgery and the Department of Speech and Hearing Sciences. The Center director is Dr. Jay Rubinstein. The director of Research is Dr. Edwin Rubel.

Research Activities

The Center supports a number of research activities related to the Hearing Research Initiative, and hearing, vestibular, and communication research at the University of Washington. For a description of current research directions at the Center please go here.

Research Programs

Several intramural laboratories are pursuing active research within the Center. A list of these laboratories and links to their activities are presented below:

The Bermingham-McDonogh Lab uses tissue-specific knockout technology to investigate what growth factors are important in the survival of spiral ganglion cells. This research provides insights into potential techniques to enhance the survival of these cells when implants are used to restore auditory function in patients.

The Feeney Lab is developing techniques for testing and diagnosing hearing loss in patients, focusing on using wideband energy reflectance to evaluate middle-ear function and development. This method allows an earlier and more accurate diagnosis of hearing complications in newborns, infants, and adults.

The Hume Lab is identifying the molecular signals that regulate the formation of hair cells and their neuronal connections during development using a combination of molecular biology, organ culture and genetic techniques. These studies will provide insights into potential strategies to treat human hearing loss.

The Oesterle Lab is studying how leukocytes, growth factors, and transcription factors promote progenitor-cell division and hair-cell differentiation in the inner ears of mammals and birds.

The Phillips Lab studies the ear's contribution to balance and vision. Researchers in this lab record from single brain cells to understand how the brain processes balance information and uses that information to stabilize the eyes and body. In addition, this laboratory tests infants and children to see how these mechanisms develop.

The Rubel Lab. This laboratory performs research into the cellular processes underlying development and plasticity of auditory information processing using anatomical, physiological, and cellular methods to examine the and mature inner ear and auditory brainstem. In vitro and in vivo preparations are used in parallel to examine the mechanisms that control growth, death and regeneration of cells and connections within the auditory system.

The Rubinstein Lab uses novel signal processing strategies to enhance function of current cochlear implant technology, and to understand the processing of auditory information in the brain. In addition, the group is developing novel instruments to evaluate auditory processing in patients.

The Stone Lab is characterizing hair cell progenitors and stem cells from the mature avian inner ear. In addition, researchers in this laboratory are evaluating the role of transcription factors in promoting cell-cycle exit and hair cell differentiation in birds.

The Tempel Lab uses molecular, genetic and electrophysiological techniques to study the functional role of potassium channels within the auditory system. The laboratory has created mice carrying targeted deletions for specific channel genes, providing insights into hearing loss and neuronal hyperactivity.

Research Facilities

Histological laboratories:

Histological facilities, available to all affiliates of the Hearing Research Center, include a cryostat, sliding microtomes, a Leitz rotary microtome, a Sorvall MT-2, a Sorvall JB4-A microtome, two ultra-microtomes, an LKB knife breaker, and one Oxford vibratome.

Microscopy Laboratories:

The facility maintains four research quality light microscopes. These include a Leitz Orthoplan II Photomicroscope with bright field, dark field, Nomarski, and fluorescence optics; a Zeiss photomicroscope with bright field, dark field, fluorescence, and Nomarski optics; and a Leitz dual-headed research microscope. In addition there are two computer-aided image analysis systems: a Bioquant and a Macintosh-based NIH Image System, both used for quantitative analysis of microscopic tissue. There is also a BioRad Model 1024 Scanning Laser Confocal Microscope equipped with UV and an inverted microscopy set-up for calcium imaging using FURA-2 and FLO-3 and other fluorescently labeled compounds. There is also an Olympus Fluoview-1000 laser scanning confocal microscope. It has an inverted Olympus IX81 microscope with 10X and 20X dry objectives, 40X and 60X oil immersion objectives, all capable of DIC. Detectors include 3 fluorescent channels and a transmitted light channel, plus spectral unmixing capability. The lasers provide lines at 405 nm, 458 nm, 488 nm, 514 nm, 543 nm and 637 nm. Additional features include scan sizes up to 4096X4096 pixels, bi-directional scanning, sequential capture, scan rotation and irregular scan regions. A darkroom with film processing units is also on site.

Electron microscopy:

Lab personnel have access to outstanding electron microscopy facilities. An NIH Multi-user Equipment Grant recently provided funds to purchase two new electron microscopes for exclusive use by a small group of participants. These were a JEOL model JEM 4200F transmission electron microscope and a JEOL model JSM 6300FE field emissions scanning microscope. The new microscopes are housed in an electron microscopy facility in the basement of the medical center. Adjoining this space is a region for ultramicrotomy, including a stall to house an ultramicrotome. Facilities also are available for scanning electron microscopy tissue preparation, including a new state of the art sputter coater and a new critical point dryer.

Tissue culture laboratory:

The Center is fully equipped to carry out organ and cell culture studies. Major equipment includes: two Muaire Class II Type A/B3 laminar flow hoods; two Sheldon 1820 C02 incubators; IEC centrifuge; Pella vibratome; Wild microscope for tissue dissection; Nikon inverted microscope with epifluorescence, Nomarski and stage incubation system; roller tube culture cabinet; and a refrigerator and freezer for tissue culture media and solutions.

Electrophysiology:

The Center has a surgical suite for small animal surgery, which is equipped with several operating microscopes, surgical lamps, instruments, and a vented perfusion system. Another series of rooms is designed to house common small laboratory animals, such as gerbils, chickens, mice, and zebrafish. Two in vivo electrophysiology laboratories are equipped with double walled IAC booth, oscilloscopes, calibrated closed field sound generation and calibration equipment. One system is used primarily for emissions research. This is supported by Macintosh and PC computers with digital signal processing boards and digital IO boards. Digital oscillators and digitally controlled attenuators are controlled by this computer. The second electrophysiology lab is used for single unit recording. These electrophysiology suites are supported by pipette pullers and other electrode fabrication facilities. Two dedicated HP Spectrum Analyzers are available for calibrations. In addition to the two in vivo electrophysiology labs, there are four in vitro labs that are fully equipped for extracellular and intracellular recording.

Cellular Neurophysiology:

This complex multi-user laboratory consists of six rooms designed and equipped to carry out state-of-the-art electrophysiology research on single cells and small groups of cells that are maintained in tissue or organ cultures. Three of these electrophysiology rigs are used for brain slice and small cell recording, Four of the rooms are equipped with computers, microscopes, and specialized electronic equipment for recording the electrical potentials and ionic changes in cells in response to manipulations of their internal or external environments. Two other rooms are equipped for tissue preparation and experimental support.

Molecular Biology Laboratory:

This lab, run by Dr. Bruce Tempel, is fully equipped for basic molecular biology, with bacterial/yeast and tissue culture abilities. Centrifuges include a Sorval SupraSpeed RC-28S, Beckman GS-15, a Nikon Optophot microscope, and a Shimadzu UV-160U spectrophotometer. There is a shared equipment room located adjacent to the lab which includes a Packard scintillation counter, shakers, UV setup, dishwashing and autoclave facilities.

Human Auditory Performance Labs:

Facilities for testing human adults and infants include three double-walled sound booths and equipment for behavioral testing, recording of evoked potentials and otoacoustic emissions.

P30 Facilities

Core facilities supported by an ongoing P-30 grant from the NIDCD are located in and administered through the Virginia Merrill Bloedel Hearing Research Center. These facilities support 4 research cores, including Human Subjects Core, an Imaging and Microscopy Core, a Computer Resources Core, and a Mouse Genetics Core.

The Human Subjects Core is jointly administered through the Center and the Department of Speech and Hearing. It provides researchers with access to an infant subject pool, a child and adolescent subject pool and a hearing and vestibular research subject pool which can be used in support of research at the University of Washington. The specific objectives of this core are 1) to provide potential infant, child and adult participants to researchers at the University of Washington in a cost efficient and effective manner.
2) To encourage collaboration among investigators. 3) To promote research in the mission areas of NIDCD by making special populations available to investigators

The Computer Resources Core provides direct technical support, software and hardware consulting and assistance, website updates and research programming in support of the research objectives of the NIDCD.

The Imaging & Microscopy Core supports the facilities of the Microscopy Laboratories and provides consulting on imaging and labeling methods, and the application of these methods to research at the center. The Facility is one component of the UWCCR's Imaging Core, which also contains a component for Functional Magnetic Resonance Imaging (fMRI).

The Mouse Genetics Core provides expert mouse husbandry for many strains mice in support of scientists pursuing research on the genetics of hearing and vestibular function.
The Mouse Genetics Core provides a centralized resource for scientific advice and technical support in the form of expert husbandry (receiving, setting up crosses, weaning, fostering, background transfers, etc), genotyping, and notification/delivery of requested mice to the users. The specific aims of the Core are:1) To provide expert mouse husbandry for various strains of mice in support of scientists whose research goals involve understanding the development and/or function of the auditory system.
2) To provide a genotyping and distribution service that includes development of PCR protocols. 3) To encourage interactions between users by sharing information on projects and phenotypes of mice under study by each user.

Library and Conference Room:

This room is equipped with journals, three computers for general use and a slide projector. The room serves as a general meeting room.

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