1975 — 1979 |
Farbman, Albert (co-PI) [⬀] Gesteland, Robert |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Intracellular Study of Olfactory and Gustatory Receptors @ Northwestern University |
0.915 |
1985 — 1990 |
Gesteland, Robert C |
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. |
Role of Cellular Organelles in Olfactory Reception @ University of Cincinnati
Recent work has shown that the physiological implications of continual olfactory receptor replacement are profound. Most of the previously published results of studies of receptor mechanisms and of coding in the primary neurons will require reevaluation. It now appears that there are two classes of receptor neurons which respond differently to chemical stimulation, the recently differentiated neurons and the mature neurons. The differences reside in the membranes of the cilia and in the capacities of the cells for spike generation. These experiments will determine the differences in response properties of the two cell types and how their responses combine in the stimulus-evoked electro-olfactogram (EOG) and epithelium impedance change. The experiments measure responses to chemical stimulation at different stages during epithelial regeneration following nerve section and necrosis ablation. The changing proportions of the different cell types during this process allows determination of the contributions of each to the response. The reasons for complex EOG waves, for two independent components of the impedance change, and for simple and complex types of single-cell spikes have never been determined. These experiments test the hypothesis that these complex responses result from simultaneous activities in different cell types. The ionic mechanisms contributing to the EOG and the impedance change will be determined using ion replacement in the isolated receptor organ. Differences in ionic components of action potentials at different stages of neuron maturity will be explored using ion replacement on tissue slice preparations. An attempt will be made to block mitosis during regeneration to produce an epithelium with cells of homogeneous maturation state. Such a preparation would simplify experimental studies and clarify their interpretation. Olfactory receptors are unique among neurons of the vertebrate nervous system in their capacity for renewal. This work will further our knowledge of the processes which occur in these cells and the mechanisms which account for the olfactory sense.
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1 |
1986 — 1990 |
Gesteland, Robert C |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Development and Regeneration Invertebrate Olfaction @ University of Cincinnati
The ability of the vertebrate olfactory system to regenerate after injury, its connective plasticity, the continual replacement of sensory neurons throughout the life of the animal and its unique embryonic origins raise fundamental questions about neuron cell biology. This project focuses on a group of issues which will have significant impact upon interpretation of anatomical, neurochemical and electrophysiologicall findings. The experiments study the details of developmental events in olfaction, central reconnection after injury and the early stages of tissue differentiation and growth. The experimental methods include powerful new techniques of immunocytochemical labeling, morphometric analysis at the ultrastructural level, excitability studies of single cell s from dissociated tissues, neurons grown in culture, and new tracer techniques for study of connectivity. All of the projects are directed to issues of developmental change and the relations to regeneration and connection. We hope to find the origins of olfactory nerve Schwann cells, how growing axons penetrate the basement membrane, the effects of odors, zinc intake and environmental challenges on the rates of synthesis of receptor membrane and neuron turnover, the changes in membrane ionophores during receptor neuron differentiation and maturation, the relationships between regenerative processes in olfactory receptors and in other axotomized neurons, whether the continually turning-over neurons form effective synapses or are resorbed without functional connection, and the developmental changes in organziation of the cholinergic bulb afferents. In conjunction with the animal experiments a new type of olfactometer will be built in prototype and tested. It will make clinical evaluation of olfactory acuity simple and precise. The program is a collaborative effort to understand development, plasticity of process, form, mechanism and connectivity in that part of the vertebrate nervous system in which change is most evident. The investigators are closely associated in the univeristy community and intensely interested in the cellular processes involved in olfactory signalling.
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0.942 |
1991 |
Gesteland, Robert C |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Confocal Microscope Imaging System @ University of Cincinnati
Confocal scanned imaging light microscopes became commercially available in 1987. There was instant excitement among the biological community. Details of cellular and subcellular structures labelled with fluorescent dyes or reflective gold deep in tissues are visualized with great clarity. Scattered light from out-of-focus tissue above and below the plane of focus is almost completely eliminated. Three dimensional reconstructions of the tissue can be developed from a series of optical images acquired as the plane-of-focus is scanned through the tissue. Non-destructive high-resolution images of living tissues labeled with voltage- and ion-sensitive dyes follow dynamic processes of cell and organelle function. Many investigations of spatial relationships which were difficult and immensely time consuming are now relatively straightforward. We are now in the second generation of instrument development. Experimental limitations of the technique are well understood. Instrumental versatility is increased. Different instruments are best suited to different investigations. Investigators now have a fairly clear understanding of which of their scientific goals can be realized more effectively and of what questions which had not been experimentally practical are now possible. This Shared Instrumentation Grant application is submitted by a group of investigators with extensive PHS grant funding a strong commitment to the application of front-edge techniques to their studies, and a realization that installation of a confocal imaging facility at the University of Cincinnati will stimulate the research effort well beyond the goals of their specific projects. The instrument proposed is well-suited for all of the investigator's projects. By sharing an instrument facility optimized for their needs an instrument that would be prohibitively expensive for a single investigator becomes accessible. Investigators are in the Departments of Anatomy & Cell Biology and of Molecular Genetics, Biochemistry & Microbiology. The faculty in these departments are among the most substantially funded in medical colleges in the United States. Projects of the investigators include studies of receptor neuron stimulus selectivity, fibroblast differences in pulmonary fibrosis, structure and dynamics of cytoskeltal elements, plasticity in the neuroendocrine system, organization of cortical neural networks, metabolic signaling by movement of intracellular lipids, and virus reactivation in nerve cells. The investigators are widely recognized for work using imaging techniques to advance understanding of structure-function relationships and have introduced major advances in research techniques. This proposal is for funds for a laser scanning confocal microscope and image analysis instrument which will advance their research efforts. The projects of each of the investigators are high-priority, health-related scientific studies in the fields of neuroscience, and cell and molecular biology.
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0.942 |
1992 — 1995 |
Gesteland, Robert C |
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. |
Voltage Dye Confocal Analysis of Olfactory Transduction @ University of Cincinnati |
0.942 |
2000 |
Gesteland, Robert C |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Clinical Evaluation of Olfaction Using a Sniff Device @ Emerging Concepts, Inc.
Smell loss is a significant health and safety problem for millions of Americans. Unfortunately, clinical assessment of smell function is not routinely performed because a rapid inexpensive and valid test of olfaction is not available. An improved test would enhance the detection and treatment of smell loss and several neurodegenerative diseases, including Alzheimer's disease. The goal of the proposed project is to develop a new test based on exploratory sniffing behavior. Preliminary studies show that people with a normal sense of smell reduce sniff magnitude when they encounter a malodor, while people who have lost their sense of small do not. The feasibility of this approach will be demonstrated by showing that the sniff test possesses psychometric and practical features that make it superior to alternative tests. Phase II funding will be used to conduct additional validity tests and to develop a commercial version of the sniff test. Development of the sniff test device will provide clinicians with a method of evaluating olfactory function that is valid irrespective of a person's age, cultural background or state of intellectual function. This test will permit standardized, widespread and routine testing of the sense of smell, and thus improve the diagnosis and treatment of smell loss. PROPOSED COMMERCIAL APPLICATIONS: Over 42 million Americans are at-risk for olfactory loss. Based on the cost of the most widely-used clinical test of olfaction (the UPSIT) an estimate of the commercial potential of an improved olfactory test is of the order of $1 billion. Since the sniff test crosses barriers of language and cultural, there is a clear opportunity to access a much larger international market, estimated at 260 million people.
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0.904 |
2002 — 2003 |
Gesteland, Robert C |
R44Activity Code Description: To support in - depth development of R&D ideas whose feasibility has been established in Phase I and which are likely to result in commercial products or services. SBIR Phase II are considered 'Fast-Track' and do not require National Council Review. |
Sniff Magnitude Ratio as a Measure of Olfactory Acuity @ Emerging Concepts, Inc.
DESCRIPTION (provided by applicant): Smell loss is a health and safety problem for millions of Americans. Assessment of smell function is not routinely performed because a rapid, inexpensive and robust test of olfaction is not available. Our SBTR Phase I grant demonstrated the feasibility of a new test of olfactory function, the sniff magnitude test. The test performed well in reliability and validity studies with adults as compared to standard tests, and proved to be superior to the UPSIT in tests with children. Because the sniff test is based on reflex-like reduction of sniffing to a malodorous stimulus, it is hypothesized that it will have advantages over standard tests that require substantial cognitive, memory and language skills. This SBIR Phase II application aims to enhance the sniff magnitude test by (1) improving the odor delivery and sniff measurement equipment and protocol, (2) reducing the cost of the test device, (3) demonstrate the utility of the test in the clinic, and (4) providing robust demonstrations of the advantages of the test with populations who have proved difficult or time consuming to evaluate with existing olfactory acuity tests.
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0.904 |