1985 — 1994 |
Tolbert, Leslie P |
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. |
Ultrastructural Development of Antennal Center
Olfactory glomeruli, which are compartments of neuropil where synaptic interactions between olfactory sensory axons and their target neurons take place, have been known for some years to be induced by the ingrowth of olfactory sensory axons. Studies in the current grant period have revealed that glial cells, the major non-neuronal cells of the nervous system, play an essential role in the olfactory-axon induced formation of olfactory glomeruli in a model system, the antennal lobe of an insect. The proposed research aims to elucidate the role that neuron-glia, and also neuron- neuron, interactions play in the construction of glomeruli, and to further our understanding of the mechanisms underlying these important developmental events. In particular, the proposed experiments will continue to test the hypothesis that glial cells act as intermediaries between the sensory axons and their eventual synaptic targets, i.e. that glial cells are "transformed" by exposure to olfactory axons and that "transformed" glia form the scaffold within which target neurons differentiate glomerular arbors. Toward this end, the experiments will: (a) determine the precise time in the development of glomeruli when glial cells must be present, (b) determine how stable is the "transformation" of glia by olfactory axons, (c) explore the expression of cell-surface and extracellular-matrix markers during development of the glomeruli, (d) determine whether the glia-defined boundaries of glomeruli represent diffusion barriers for ions or for other potential factors influencing differentiation, and (e) discover the extent of glial cell death and determine its significance in the creation of the glomerular scaffolds. In mammals, recent findings suggest that glial cells may play a role in the early compartmentation of the central nervous system in a manner similar to that observed in the antennal lobe of the insect. In the long run, understanding the roles and mechanisms of intercellular interactions in the more accessible insect system will offer insights into interactions in mammalian systems and may reduce the need for experimentation in mammals.
|
0.928 |
1995 — 1999 |
Tolbert, Leslie P |
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. |
Core-- Confocal and Electron Microscopy
It is proposed to consolidate and support a core facility that will provide technical expertise and well-maintained, up-to-date equipment for electron- microscopic and light-microscopic studies associated with this Program Project. The instrumentation and physical facilities are already in place. Other NIH-supported investigators in addition to the participants in this Program Project will benefit from this facility.
|
0.928 |
1995 — 2005 |
Tolbert, Leslie P |
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. |
Intercellular Interactions in Developing Glomeruli |
0.928 |
1997 |
Tolbert, Leslie P |
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. |
Imaging Facility For Neurobiology
With the current application, five faculty in the Division of Neurobiology at the University of Arizona seek to establish a state-of-the-art biological imaging facility to enhance their studies of the development and functional organization of experimentally favorable insect nervous systems. The Division's current Imaging Facility, staffed by a full-time Assistant Staff Scientist, has a Bio-Rad MRC-600 laser scanning confocal microscope, which the five Major Users of this proposal use heavily for NIH-funded research. The MRC-600 is inefficient compared to newer confocal systems and is so popular that one now has to sign up for time 3 - 4 weeks in advance, making the confocal microscope the rate-limiting step in most of our experiments. Moreover, some confocal-microscopy projects have advanced to the point where additional resolution, the capability to visualize fluorescently labeled structures across a broad range of brightness, and the capability to image living preparations over long time periods under very low light levels would enhance our efforts. Therefore, the PI proposes to upgrade the MRC-600 confocal microscope to a MRC-1024, and to purchase a deconvolution microscopy system. The confocal upgrade will provide a larger pixel array for larger fields of view, more filter sets and three photomultiplier tubes for improved detection of multiple fluorophores, and a more efficient computer and software package. Deconvolution, while superficially similar to confocal microscopy in its ability to produce fluorescence images of significantly higher resolution than a standard fluorescence microscope, differs from the confocal microscope in two important ways: rather than rejecting out-of-focus light with a pinhole in the detector, it collects as much light as possible from the objective lenses and uses it to mathematically reconstruct the bright object; and rather than using a photomultiplier tube, which is noisy and whose output is not linearly related to input, it uses a CCD camera for sensitive, linear reporting. Thus, the deconvolution system will meet many of our emerging needs.
|
0.928 |
1999 |
Tolbert, Leslie P |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Training Program in Insect Science |
0.928 |
2001 — 2005 |
Tolbert, Leslie P |
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. |
Core-- Microscope Facility
DESCRIPTION: The Confocal and Electron Microscopy Facility is equipped for electron microscopy (EM) and light microscopy (LM) including confocal and live-cell imaging, including time-lapse video and calcium imaging systems. It has also been expanded during the previous funding period to include a Computer Imaging Facility for image processing and analysis. All 5 projects will use the LM-based systems and 3 will use EM. In addition to the equipment, the facility provides training and technical support. The facility is overseen by Dr. Leslie Tolbert and employs three staff members: 1) a Master's level Senior Research Specialist, Ms. Jansma, (60% effort on PPG and 40% for the Division) technically expert in EM and confocal microscopy, she maintains all of the scopes, trains new users and helps to develop protocols. 2) a part-time research technician, Ms. Potts (20% effort here and 80% effort on Project 2) provides training and assistance with the confocal and live-cell systems. 3) a part-time computer expert, Mr. Yuhas (75% effort on PPG and 25% effort in the Division) maintains computers, installs upgrades and trains users in software.
|
0.928 |
2001 — 2005 |
Tolbert, Leslie P |
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 of Sexually Dimorphic Olfactory Glomeruli
Primary olfactory neuropils in both vertebrates and invertebrates are characterized by arrays of synaptic glomeruli, each of which processes information about particular attributes of odorous stimuli; but little is known about how these striking spatial arrays develop. In the moth Manduca sexta, the olfactory neuropil comprises 64 glomeruli that appear to be similar in males and females, and two to three specialized and easily recognizable glomeruli that are unique to each sex and that process information about odors important for reproduction. Previous experiments have demonstrated that male-specific group of specialized glomeruli, including recruitment of female target neurons into that circuitry. Furthermore, even if entering the brain from an abnormal position, those male-specific axons find the correct target site. Thus, the sexually dimorphic olfactory system of Manduca offers a special opportunity to investigate a central question in olfactory development: what cellular interactions underlie the development of the array of glomeruli. The proposed project addresses the question, with two specific aims: (1) to explore aspects of the "address" that male-specific olfactory receptor axons recognize in the target olfactory neuropil and to determine whether synaptic interactions between those axons and particular target neurons underlie the dendritic morphology that the axons induce in those neurons; and (2) to determine the role of nitric oxide, a gaseous intercellular signaling molecule which appears to be released by developing olfactory axons, in the development of both sexually isomorphic and sexually dimorphic glomeruli in the antennal lobe. The project, taking advantage of the relative cellular simplicity of the moth olfactory system, and using state-of-the-art microscopical methods in addition to electrophysiological, biochemical, and molecular biological approaches is expected to provide insights into the development of less accessible mammalian olfactory systems.
|
0.928 |
2010 |
Tolbert, Leslie P |
C06Activity Code Description: To provide matching Federal funds, up to 75%, for construction or major remodeling, to create new research facilities. In addition to basic research laboratories this may include, under certain circumstances, animal facilities and/or limited clinical facilities where they are an integral part of an overall research effort. |
College of Medicine Phoenix Campus Vivarium Phase I Construction
DESCRIPTION (provided by applicant): The University of Arizona College of Medicine - Phoenix in Partnership with Arizona State University (COM-P) recruited its first new faculty to the Phoenix Biomedical Campus in 2006, and currently has 22 faculty with research laboratories in the Arizona Biomedical Collaborative 1 (ABC 1). Animal research by these faculty is currently conducted at various AAALAC-approved vivarium facilities throughout the Phoenix metropolitan area. The specific aim of the present proposal is to support construction of a 12,100 DGSF vivarium on campus to meet existing and future scientific needs. This represents Phase One of a larger vivarium project currently planned for the Phoenix Biomedical Campus along with construction of the Health Sciences Education Building and the ABC 2 research building. The COM-P Phase One Vivarium will include animal holding rooms with a total capacity of 4,158 mouse cages and 1,200 rat cages for rodent housing. Rooms will be provided for breeding of transgenic mice lines, specialized behavioral assays of rats and mice, animal biosafety level 2 (ABSL2) procedures in mice, quarantine of rats and mice, and segregation of rodents returning to the vivarium from laboratories. Specialized suites are included for behavioral analyses, ABSL2 containment and decontamination, and small animal imaging and irradiation. In addition, areas will be dedicated to clean and dirty cage, food and bedding storage;animal receiving;euthanasia and veterinary procedures;surgical facilities, and procedure rooms for physiological measurement, telemetry, injections, blood and tissue collection, and other in vivo procedures. The vivarium will house rodents in Innovive(R) individually ventilated, disposable (recyclable) caging systems. In addition, locker rooms with restrooms and showers, a staff room and office are provided. Fixed, major equipment requested includes: two Class 2, Type B2 fully exhausted biosafety cabinets, seven Class 2, Type A2 biosafety cabinets, an autoclave, examination lamps, and a reverse osmosis Hydropak water pouch production system. In accordance with the Initiative on Climate Change, signed by the participating University Presidents, this project will pursue LEED Silver certification with sustainability concepts, including recycling, energy efficiency, reduced water use and sustainable site and open space plans. The COM-P Phase One Vivarium will provide much needed facilities in support of existing PHS research at a new and rapidly growing medical college located in the fifth largest U.S. city. Timely award and construction of the project will create or retain 126 jobs, with ongoing operations of the facility creating or retaining 18 jobs. The best and only way to assure optimal standards of experimental animal care required for our PHS-supported research efforts is to construct this dedicated laboratory animal vivarium serving the Phoenix Biomedical Campus.
|
0.928 |