Area:
Molecular Biology, Neuroscience Biology
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High-probability grants
According to our matching algorithm, Janet L. Cyr is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2001 — 2002 |
Cyr, Janet L |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Recombinant Antibodies Against Hair-Cell Proteins @ West Virginia University
DESCRIPTION (provided by applicant): Damage to the receptor cells of the inner ear, the hair cells, is a common underlying cause of hearing impairment. A complete understanding of hair-cell function requires the identification and characterization of the proteins that confer the cell?s unique properties, including proteins present in the hair bundle, the cell?s mechanosensitive organelle. Such a biochemical characterization has been impeded by the scarcity of material available for analysis. The generation of specific labeling reagents, for example monoclonal antibodies, should provide the means to overcome this obstacle: immunological tools will permit us to identify critical hair-cell and hair-bundle proteins, to study their intracellular targeting, and to pinpoint other molecules with which they interact. Recombinant antibodies displayed on the surface of filamentous bacteriophage should allow us to sidestep many of the difficulties inherent in obtaining conventional antibodies against low-abundance proteins. Production of recombinant antibodies does not in principle require immunization, large numbers of antibodies can be isolated, and sophisticated selection schemes for isolation of interesting clones can be devised. Over the past decade, substantial progress has been made in the generation and manipulation of recombinant antibodies, however their application in the study of low-abundance proteins has not been thoroughly tested. Our proposed studies will extend this methodology to the study of rare proteins - in particular, those present in hair cells and hair bundles. To obtain tools for the study of hair-cell and hair-bundle proteins, including components of the transduction apparatus, we will use a bacteriophage-displayed library of recombinant antibodies directed against inner-ear proteins. We will isolate antibody-bearing bacteriophage that recognize subclasses of saccular hair-cell proteins; such antibodies will provide the necessary reagents to characterize hair-cell and hair-bundle constituents and provide a means to further understand the molecular events that result in a functional, extraordinarily sensitive mechanoreceptive cell.
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1 |
2004 — 2007 |
Cyr, Janet L |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Myosin-1c and the Hair-Cell Transduction Apparatus @ West Virginia University
DESCRIPTION (provided by applicant): The detection of mechanical stimuli by hair cells, the sensory receptors cells of the inner ear, underlies our senses of hearing and balance. Despite substantial research efforts, the molecular basis of hair-cell mechanotransduction is poorly understood. In particular, little progress has been made in the identification and characterization of the proteins that constitute the hair-cell transduction machinery. Substantial data indicate that one protein of the vestibular hair-cell transduction machinery has been identified. This protein, an unconventional myosin called myosin-1 c, serves as the motor protein that powers slow adaptation, which maintains the hair cell's sensitivity to small stimuli. In its role as the adaptation motor, myosin-1c must interact with the other components of the transduction machinery including the elusive mechanically-gated transduction channel. Our long-term goal is to understand how myosin-1c and other hair-cell transduction proteins assemble into a mechanosensitive complex and how they function in our senses of hearing and balance. The objective of this application is to extend our recent studies that examined the interaction of myosin-1c with proteins located at stereociliary tips, the site of hair-cell transduction and to exploit this interaction to isolate other components of the transduction apparatus. Our central hypothesis is that the neck domain of myosin-1 c binds to constituents of the transduction apparatus and that myosin-1 c's calmodulin light chains regulate this interaction, in addition to modulating the myosin's motor activity. In this proposal we will (1) define the portion of the myosin-lc neck responsible for binding to other transduction components; (2) examine the role of the neck domain in myosin-1 c motor activity and (3) use the myosin-lc neck region as a tool to identify and characterize other transduction components. These studies will provide insight into the molecular basis of hair-cell mechanotransduction, which is critical for an understanding of how we sense both sound and head position.
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1 |