On-Line Control of Cell Reduction State
{'Code': '15030000', 'Directorate': {'Abbreviation': 'TIP', 'LongName': 'Dir for Tech, Innovation, & Partnerships'}, 'Division': {'Abbreviation': 'TI', 'LongName': 'Translational Impacts'}}
{'SignBlockName': 'Ritchie B. Coryell', 'PO_EMAI': None, 'PO_PHON': None}
The development of on-line, sensor-based control systems capable                of directly monitoring and responding to biochemical events                     inside a cell would be a major advance in the regulation of the                 complex biochemical reactions needed to synthesize commercial                   products.  Using the butanol fermentation as a model system in                  Phase I, the feasibility for process control was demonstrated by                running continuous fermentations in which the reducing agent,                   benzyl viologen, was successfully used to control culture                       fluorescence at a predetermined set point.  It is the premise of                the Phase II project that using additives to control the                        reduction state of the cell is a generic phenomenon that is                     likely to result in novel operating strategies for a broad range                of fermentation and cell cultivation processes.  The research                   program is designed to study the relationship between the                       intracellular reduction state as measured by the ratio of                       ıNAD(P)H/(NAD(P) + NAD(P)H! and enhanced product formation in                   several broad types of processes.  Building upon the results of                 Phase I, the butanol fermentation will be employed as the system                to quantify product formation as a function of the reduction                    state in anaerobic procaryotes.  Recombinant E. coli will be used               to study aerobic procaryotic cells to determine the relationship                between the reduction state and the optimal expression of                       genetically engineered polypeptides and proteins.  Eucaryotic                   cells will be studied by using hybridomas as the model system to                examine the production of monoclonal antibodies as a function of                cell reduction state.  In all three systems, the concentration of               intracellular NAD(P)H will be used as the control variable for                  regulating product biosynthesis.                                                                                                                                Sophisticated systems for monitoring and controlling fermentation               and mammalian cell cultivation processes are needed for the                     scale-up and commercial production of many products of                          biotechnology, such as plasminogen activator, monoclonal                        antibodies, interfon, and interleucon-2.  The currently available               on-line process sensors are few in number (i.e. temperature, pH,                dissolved oxygen, redox, etc.) and limited by the fact that they                measure environmental variables and not the intracellular                       characteristics.  None of the currently available on-line process               sensors are able to measure intracellular metabolism directly.                  The development of on-line process sensors are able to measure                  intracellular metabolism directly.  The development of on-line,                 sensor-based control systems capable of directly monitoring and                 responding to biochemical events inside a cell would be a major                 advance in the regulation of the complex biochemical reactions                  needed to synthesize commercial products.  The objective for the                research is to use the recently developed instrumentation for                   monitoring the health of cells.  This ability to measure changes                directly in intracellular metabolism will be the motivation for                 developing innovative process control techniques.  It is                        anticipated that the proposed research will ultimately result in                                               -2-                                                                                                                                                                                                              improved process control with increased productivity and lower                  costs for a broad range of commercial fermentation and cell                     cultivation processes.
{'FirstName': 'William', 'LastName': 'Armiger', 'PI_MID_INIT': 'B', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'William B Armiger', 'EmailAddress': None, 'PI_PHON': None, 'NSF_ID': '000231132', 'StartDate': '10/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'BioChem Technology Inc', 'CityName': 'Malvern', 'ZipCode': '193551303', 'PhoneNumber': '2156478610', 'StreetAddress': '66 Great Valley Parkway', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Pennsylvania', 'StateCode': 'PA', 'CONGRESSDISTRICT': '06', 'CONGRESS_DISTRICT_ORG': 'PA06', 'ORG_UEI_NUM': None, 'ORG_LGL_BUS_NAME': None, 'ORG_PRNT_UEI_NUM': None}
{'Name': None, 'CityName': None, 'StateCode': None, 'ZipCode': None, 'StreetAddress': None, 'CountryCode': None, 'CountryName': None, 'StateName': None, 'CountryFlag': None, 'CONGRESSDISTRICT': None, 'CONGRESS_DISTRICT_PERF': '""'}
{'Code': '5373', 'Text': 'SBIR Phase II'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8722876.xml'}