We postulate that there are super-control systems in the bacteria cell (perhaps about 20), each of which involves large numbers of genes and enzymes that are related in a functional sense (the domain), and each of which is controlled by a signal molecule, the alarmone, for the particular domain. The synthesis of the alarmone is coupled to a particular stress in the bacteria (e.g., ppGpp accumulates when translation stops due to an amino acid deficiency) and the alarmone then serves to rebalance the cell metabolism (economy) in response to the particular stress. Our main objectives are: 1) To identify as many of these alarmones and their domains as possible; 2) To develop new methods for identifying alarmones; 3) To establish the role of modified bases in tRNA (such as pseudouridine) in regulation and their relation to super-control systems; 4) To develop methods for studying modified bases in tRNA; 5) To clarify the nature of the complex promoters in the DNA of genes and operons as related to the functioning of alarmones and modified base control. The methods developed in this project and the new control molecules identified should clarify the understanding of fundamental aspects of the regulation of metabolism in both bacteria and higher organisms.
