Regulation of Amino Acid Biosynthesis
{'Code': '08070100', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Philip Harriman'}
The enzyme aspartokinase plays a central role in bacterial amino                acid biosynthesis, and its activity is attuned to the                           physiological needs of the bacterium by complex control                         mechanisms.  Bacillus subtilis has two aspartokinases, one of                   which (aspartokinase I) is regulated by the cell wall constituent               diaminopimelate, while the other (aspartokinase II), the major                  focus of this research, is controlled by lysine and is unusual in               being composed of two different types of subunits which are                     independently translated from in-phase overlapping genes.  These                and their control regions have been cloned and their nucleotide                 sequence has been determined.  This proposal aims to apply the                  sequence information to the study of the mechanisms that control                aspartokinase synthesis and of the relationship between structure               and function of the enzyme itself.  The proposed research will                  use oligonucleotide directed mutagenesis to alter specific sites                in the control regions as well as in the genes encoding the                     protein structure, in the expectation that the study of these                   structural perturbations will reveal the mechanisms that underlie               control and function.  Another aim is the sequencing of the genes               that surround the genetic locus of aspartokinase II and the                     elucidation of their regulatory and metabolic relationship.                                                                                                     Bacillus subtilis, the species of bacterium under study in this                 proposal, has two modes of growth, vegetative under normal                      environmental conditions, and sporulation under conditions of                   starvation or other types of stress.  The latter process results                in the formation of highly durable spores which can be dispersed,               and can subsequently germinate when and where conditions permit                 vegetative growth.  Vegetatively growing bacteria, upon receiving               specific stimuli to begin sporulation, must alter their entire                  internal physiology to meet the requirements of the new mode of                 growth.  Certain key enzymes, which play different physiological                roles under the two different modes of growth, are thus under a                 very complex series of controls, which permit the transition of                 the bacterium from vegetative growth to sporulation.  This is a                 proposal to elucidate the mechanisms of these controls; it could                possibly reveal previously unknown mechanisms of control of gene                expression.  The transition of Bacillus cells from vegetative                   growth to sporulation is a developmental switch which can serve                 as a conceptual model for the differentiation of embryonic                      tissues in higher organisms.  The work in this proposal may thus                shed indirect light on the latter process.
{'FirstName': 'Henry', 'LastName': 'Paulus', 'EmailAddress': 'paulus@bbri.org', 'StartDate': '08/15/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Boston Biomedical Research Institute', 'CityName': 'Watertown', 'ZipCode': '024722829', 'PhoneNumber': '6179268040', 'StreetAddress': '64 Grove Street', 'CountryName': 'United States', 'StateName': 'Massachusetts', 'StateCode': 'MA'}
{'Code': '1112', 'Text': 'Genetic Mechanisms'}
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8803644.xml'}