This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our research is focused on molecular and supramolecular structures that facilitate communication between neurons at the chemical synapse and how such structures are perturbed in neurological disease. We are particularly interested in the architectural arrangement of signaling molecules and enzymes, and characterizing the ways in which such molecular assemblies are formed and undergo changes during synaptic transmission and modulation. Our approach is to investigate individual proteins using x-ray and electron crystallographic methods and to combine this information with EM images obtained via 3-D reconstruction of supramolecular assemblies and tomographic analysis of the intact chemical synapse. Our long-term goal is to construct a dynamic molecular and architectural map for the chemical synapse that will help to understand synaptic formation, transmission and plasticity. Using electron tomographic methods we have begun to study the architecture of the chemical synapse in cultured neurons. Our first goal is to establish the common architectural elements present at the synapse and to identify the molecules involved using specific antibody labeling or genetic tagging. Subsequently, we will perform field potential stimulations coupled with cryogenic trapping to investigate the dynamic processes involved in synaptic transmission. Ultimately we plan to study long-term, stimulation dependent, synaptic changes in the hopes of gaining insight into the architectural elements underlying synaptic plasticity. FUNDING

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000592-41
Application #
8362548
Study Section
Special Emphasis Panel (ZRG1-CB-J (40))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
41
Fiscal Year
2011
Total Cost
$21,276
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
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