E 4 - Martin Thanbichler

Adaptive evolution of cellular differentiation programs in the alpha-proteobacterium Hyphomonas neptunium








Prof. Dr. Martin Thanbichler

Philipps-Universität Marburg, Faculty of Biology

Hans-Meerwein-Straße 4, 35043 Marburg

+49 6421 - 2821624




Research summary:

In response to ever-changing environments, bacteria have evolved a large diversity of morphologies and life cycles, thereby ensuring optimal fitness in the ecological niche they inhabit. The goal of this proposal is to study the evolutionary plasticity of cellular signaling networks by comparing the pathways controlling development in the closely related but morphologically distinct alphaproteobacteria Hyphomonas neptunium and Caulobacter crescentus. Whereas the stalked bacterium C. crescentus is a well-studied bacterial model organism, using two-component signaling to regulate cell cycle progression and morphogenesis, the stalked budding species H. neptunium has not been investigated at the molecular level to date. In the first funding period, we have developed a comprehensive genetic toolbox for H. neptunium. Building on this work, we have characterized chromosome organization and segregation to establish reliable markers for cell cycle progression. In doing so, we have identified a novel two-step mechanism of DNA segregation in bacteria. In parallel, we have dissected the two-component signaling network regulating H. neptunium cell cycle progression and development and characterized its output using global transcription factor binding assays and gene expression studies. Our studies revealed that although the key components of the cell cycle-regulatory network identified in C. crescentus are conserved in H. neptunium, the overall function and connectivity of the network has changed. To identify new players in the H. neptunium system, we have generated a comprehensive library of mutants with deletions in all of the 47 non-essential two-component signaling proteins encoded in the H. neptunium genome. Screening this resource for cells with developmental phenotypes, we have identified a conserved but so-far uncharacterized singledomain response regulator (MocR) whose inactivation results in severe developmental defects.

Notably, while establishing motility assays to phenotypically analyze the mutant strains, we discovered that H. neptunium regulates motility not only as a function of the cell cycle but also in response to the osmolarity of the surrounding medium, although it lacks a generic chemotaxis apparatus. For the second funding period, we propose to perform an in-depth study of the newly identified single-domain response regulator MocR to clarify its function in H. neptunium and other alphaproteobacterial species. Moreover, we will investigate the machinery involved in the metabolism or sensing of the second messenger d-di-GMP, which is predicted to play a critical role in the cell cycle regulatory machinery based on on comparison to C. cresenctus. Finally, we will study the integration of cell cycle and environmental signals by investigating the mechanism underlying the osmoregulation of H. neptunium motility.