Gene Shut-Off Mechanisms in Bacteriophage Infection
{'Code': '08070100', 'Directorate': {'LongName': 'Direct For Biological Sciences'}, 'Division': {'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Philip Harriman'}
Programmed sequences of gene expression are ubiquitous in                       biology. None is completely understood, and, in particular,                     very little is known about mechanisms by which genes are                        sequentially shut off. This project will analyze sequential                     gene shut-off during infection of Bacillus subtilis by                          bacteriophage SPO1. In the initial experiments, two categories                  of genes will be studied, the host rRNA genes, which are not                    shut off during infection, and the SPO1 early genes, which are                  completely shut off by a few minutes after infection. First the                 two types of promoters will be tested to confirm that the                       difference in shut-off behavior of the genes resides in their                   promoters. Promoters from representatives of each category will                 be isolated and integrated into the host chromosome, each at                    the same site so each controls transcription of the same                        reporter gene. Cells containing the different cloned promoters                  will be infected by wild-type SPO1, and the time and extent of                  shut-off of each promoter will be measured by pulse-labeling                    the reporter gene transcripts. A possible role of the unusual                   base, hmUra, will be explored by cloning certain promoters in                   the SPO1 genome, and assaying them in the same way. Then, the                   sites within the promoters that cause some to be shut off,                      while others are not, will be identified. Chimeras will be                      formed between promoters with different regulatory                              specificities, and their regulation will be assayed in the same                 way as above. Where appropriate, deletion analysis will be used                 to confirm the conclusions drawn from analysis of chimeras.                     Once these initial experiments are completed, similar                           experiments will be performed with representatives of other                     categories of genes, which are turned off at different times                    during infection, and which therefore respond to different                      shut-off mechanisms. However, it is not anticipated that these                  additional experiments can be completed within this project                     period.                                                                                                                                                         When a virus infects a bacterial cell, a complex series of                      changes in gene expression occurs. Some, but not all, of the                    host cell's genes are turned off. The virus'es own genes are                    turned on in a very strictly controlled order; deviation from                   this order results in partial or complete failure of the                        infection process. As part of this strictly controlled series                   of events, particular viral genes are also turned off at                        closely specified times.  It is emerging from some of Dr.                       Stewart's prior studies that close control of turn-off of                       certain viral genes is just as critical for the success of the                  infection as is control of the time of turn-on of other viral                   genes.  Over the last 30 years a great deal has come to be know                 about mechanisms of specific gene turn-on, but as yet virtually                 nothing is known about mechanisms of specific gene turn-off.                    This is a proposal to elucidate some of these important but as                  yet obscure mechanisms.
{'FirstName': 'Charles', 'LastName': 'Stewart', 'EmailAddress': 'crs@bioc.rice.edu', 'StartDate': '10/01/1988', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'William Marsh Rice University', 'CityName': 'Houston', 'ZipCode': '770051827', 'PhoneNumber': '7133484820', 'StreetAddress': '6100 MAIN ST', 'CountryName': 'United States', 'StateName': 'Texas', 'StateCode': 'TX'}
[{'Code': '1156', 'Text': 'MICROBIAL GENETICS'}, {'Code': '9145', 'Text': 'SPECIAL PROGRAMS-RESERVE'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1988&All=true', 'xml': '8801703.xml'}