Bacterial adaption and differentiation
All cells are polarized and contain proteins that localize asymmetrically to specific subcellular regions. In bacteria as well as in eukaryotic cells, polarized proteins are important for fundamental cellular processes such as cell division, growth, motility and differentiation. We have as a working hypothesis that streamlined natural cells as well as synthetic cells depend on some level of subcellular organization for optimal function. Therefore, the overall goal of our work in synthetic microbiology is to generate a module for regulating dynamic cell polarity in streamlined natural cells as well as in synthetic cells.
For most dynamically localized proteins, the localization pattern changes in a cell cycle dependent manner. An exception to this general rule are motility proteins in M. xanthus that localize dynamically to the cell poles in a cell cycle-independent manner, i.e. during a cellular reversal motility proteins localizing to the lagging cell pole switch to the new lagging cell pole and proteins and the leading cell pole switch to the new leading cell pole. The specific goal of our synthetic microbiology is to identify and characterize the components of the regulatory system that underlies the dynamic polarity of motility proteins in M. xanthus. On the basis of this system, we aim to define a minimal module for regulation of dynamic cell polarity in bacteria and to establish this system in other microorganisms as well as in synthetic cells. As part of this research, we are addressing a more fundamental question, i.e. are cell polarity systems modular? In other words, can these systems be transferred between organisms and still function? Or are they so tightly integrated with host cell physiology that function is restricted to the original host?
The regulatory system that controls polarity of motility proteins in M. xanthus is built around the MglA, MglB and RomR proteins, which interact to define the leading/lagging polarity axis. MglA is a small Ras-like GTPase that functions as a nucleotide-dependent molecular switch to regulate motility in M. xanthus. The MglB protein functions as a GTPase activating protein (GAP) and converts active MglA-GTP to the inactive MglA-GDP. Between reversals MglA-GTP localizes to the leading cell pole together with RomR while MglB localizes to the lagging cell pole also together with RomR. MglA-GTP between reversals sets up the correct polarity of dynamically motility proteins. In response to signaling activity of the Frz chemosensory system MglA, MglB and RomR are released from the poles and then relocate to the respective opposite poles. In total, this results in an inversion of the leading/lagging polarity axis and the relocation of dynamic motility proteins.
Currently, we focus on defining the parts of this cell polarity system and on elucidating how the various proteins interact. In parallel, we are attempting to establish the system in heterologous hosts.