Pattern formation is a key process in establishing the shape of a living organism, and it rests on intercellular communication. Patterning mechanisms remain poorly understood, primarily due to the complex organization of the eukaryotic systems in which they have been traditionally studied. Recently, it has been discovered that cells of E. coli and other gram-negative bacteria under certain conditions become sources of attractants. Chemotactic interactions in gradients of self-generated attractant produce different dynamically maintained multicellular structures, which, in turn, self-organize into spectacular spatial patterns. Chemotactic aggregation and self-organization in bacterial populations is a beautiful example of how an extremely regular and complex spatial pattern can be created even in the absence of a specialized genetic program encoding spatial information. Collective interactions by themselves--resulting from elementary processes such as excretion and degradation of a signal, motile behavior, and growth of individual bacteria--can encode nontrivial structure formation, more complex than could be anticipated from the behavior of a individual bacteria carrying out its own genetic program. We propose to study this phenomenon, both experimentally and by comparing to first principles theoretical analysis. Since the chemotactic behavior of individual bacteria has been quantitatively characterized for E. coli, a complete theory for the bacterial dynamics can be written down, with no free parameters. Discrepancies between the theory and experiments can thus be directly traced to uncertainties in the biochemistry. A principal goal of this research proposal is to use such models to rigorously find out how (local) microscopic rules of bacterial behavior and physiology translate into multicellularity and patterns on a (global) macroscopic scale. An example that we propose to analyze are slugs, large groups of E. coli which migrate and behave like a coherent, multicellular organism. The proposed work has two interconnected parts. Experiments include advanced imaging, standard methods of biochemistry and molecular genetics and will be aimed at investigating dynamics of essential elements of this phenomenon. In parallel, theoretical work (including both analytical methods and computation) will be conducted to construct models, which will both quantify and focus the experimental research.
| Nguyen, Baochi; Upadhyaya, Arpita; van Oudenaarden, Alexander et al. (2004) Elastic instability in growing yeast colonies. Biophys J 86:2740-7 |
| Mittal, Nikhil; Budrene, Elena O; Brenner, Michael P et al. (2003) Motility of Escherichia coli cells in clusters formed by chemotactic aggregation. Proc Natl Acad Sci U S A 100:13259-63 |
