Spatio-temporal oreganization of proteins and mRNAs: the bacterial cell as a model system
The central role that signaling proteins play in growth regulation and cancerous transformation and the complexity of the signaling cascades in higher organisms raises the need for simple model systems. Bacterial systems provide such models, as their studies reveal, time and again, universal principles that are applicable to both prokaryotes and eukaryotes. Being fascinated by molecular mechanism and by the simplicity and elegance of bacterial systems, we use E. coli to ask fundamental questions that concern signaling strategies. For example: Where do signaling proteins meet in the cell? What kind of complexes do they form? What regulates association and dissociation of the signaling complexes as the signal progresses?
Our results imply that signal transduction in bacteria involves dynamic localization of proteins to different compartments, such as the cytoplasm, the inner membrane and the poles. Although the idea that mechanisms underlying signal transduction must involve dynamic subcellular localization of regulatory and structural proteins in all cells is gaining support, the principles that govern recruitment to certain cellular compartments are poorly understood.
How do proteins localize to particular sub-cellular domains? We have recently shown that mRNAs in E. coli are targeted to the future destination of their encoded proteins. In contrast to the view that transcription and translation are coupled in bacteria, we could show that subsequent to their synthesis, mRNAs are capable of migrating to particular domains in the bacterial cell in a translation-independent manner.
For the above studies we use a variety of experimental approaches: genetics, biochemistry, fluorescence microscopy and computation biology.
A novel sensory system involved in bacterial pathogenesis
Urinary tract infection (UTI) is the most common form of extraintestinal E. coli infection, and uropathogenic E. coli (UPEC) is the most frequent cause for UTI. Given the paucity of vaccine developments and the increasing rate of antibiotic resistance, new avenues to treat UTI should be explored.
We identified a novel sensory system in a uropathogenic E. coli (UPEC) strain, whose occurrence is linked to virulence. Knockout of this system from the UPEC chromosome reduces the virulence capacity. Using microarray analysis, we identified UPEC genes whose expression is affected by this system. Significantly, a large percentage of these genes are associated with pathogenesis (cell adherence, hemolysin, biofilm formation and toxin genes). We hope that our studies will shed light on new virulence strategies and lead to the development of specific anti-virulence interventions.