Abstract of Current Research
Programmed cell death (PCD), defined as an active process that results in cell suicide, is recognized as an essential mechanism in multi-cellular organisms. In 1996, we reported on the first described prokaryotic chromosomal PCD system. That was the Escherichia coli mazEF regulateable chromosomal toxin-antitoxin module in which mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, that overcomes the lethal effect of MazF. Since 1996, we have made considerable progress in understanding this system. We have characterized the genetic, biochemical, and regulatory properties of mazEF, identified various stressful conditions and antibiotics that trigger PCD through this system, crystallized the antitoxic protein MazE and determined its 3D structure and thermodynamic properties, and identified a role for mazEF in preventing phage spread .
Currently, we are extending this research in some other novel directions: (a) Characterization of the mazEF-mediated PCD network of E.coli (b) Generation of a new class of antibiotics that will directly activate mazEF-mediated PCD; (c) The relation of mazEF-mediated PCD to two other characteristics of multicellular organisms: (i) Communication ,and (ii) Differentiation. Our integrative research on how these characteristics may be inter-related should contribute to our understanding of that fundamental biological phenomenon, the multi-cellular behavior of bacterial cultures.