Regulation of Contractility in Skeletal Muscle
{'Code': '08090000', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'IOS', 'LongName': 'Division Of Integrative Organismal Systems'}}
{'SignBlockName': 'Vincent P. Gutschick', 'PO_EMAI': None, 'PO_PHON': None}
The goal of this research is to elucidate the mechanisms                   of interaction of the proteins that make up the thin filaments                  of striated muscle:  in particular, to determine the physical                   and molecular basis of cooperative interactions between the                     troponin-tropomyosin units which extend the length of the thin                  filaments of striated muscle.  Skinned muscle fibers are used                   as experimental material because these regulatory proteins and                  their environment can be manipulated.  Turnover rates of the                    thin filament regulatory proteins will be measured to gain                      insight into the intermolecular forces which hold the regulatory                strands together and in place, and to establish conditions for                  the nondestructive replacement of proteins.  The regulatory                     proteins,troponins (C,I, and T) and tropomyosin, will be                        exchanged or extracted and replaced with chemically modified                    forms, genetically different forms, and forms labeled with                      fluorescent or electon opaque probes.  The hypothesis that rigor                crossbridges activate thin filaments will be tested by decorating               them with irreversibly bound myosin fragments.  An apparatus used               in solution mixing, protocol execution, and data collection                     is automated and under computer control.   A similar apparatus                  built into a spectrofluorometer correlates data from                            fluorescent molecular probes with tension data.  The cooperative                regulation of thin filaments will be modeled using the classical                formalism for allosteric proteins (Monod el al., l965) and an                   "induced shift" model.  By comparing experimental calcium                       concentration vs tension and substrate vs tension curves from                   control, extracted, and experimentally reconstituted fibers with                the model predictions, new insights into potential mechanisms of                thin filament regulation should be obtained.                                         Although the mechanisms that regulate the contraction                      of striated muscle have been the object of much study, much                     remains to be learned at the molecular level of how each of the                 proteins of the contractile apparatus is involved and how these                 proteins interact in the process of shortening.  This research                  will extend our fundamental knowledge of the function of these                  important muscle proteins.
{'FirstName': 'Philip', 'LastName': 'Brandt', 'PI_MID_INIT': 'W', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Philip W Brandt', 'EmailAddress': 'pwb 3@columbia.edu', 'NSF_ID': '000093744', 'StartDate': '09/01/1987', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Columbia University', 'CityName': 'NEW YORK', 'ZipCode': '100277922', 'PhoneNumber': '2128546851', 'StreetAddress': '615 W 131ST ST', 'StreetAddress2': 'MC 8741', 'CountryName': 'United States', 'StateName': 'New York', 'StateCode': 'NY', 'CONGRESSDISTRICT': '13', 'CONGRESS_DISTRICT_ORG': 'NY13', 'ORG_UEI_NUM': 'F4N1QNPB95M4', 'ORG_LGL_BUS_NAME': 'THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK', 'ORG_PRNT_UEI_NUM': None}
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[{'Code': '1117', 'Text': 'CELLULAR PHYSIOLOGY'}, {'Code': '1141', 'Text': 'PHYSIOLOG & STRUCTURAL SYS'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1986&All=true', 'xml': '8620367.xml'}