Little is known about the mechanisms determining cell shape, and the larger questions concerning morphogenesis are the same in prokaryotic and eukaryotic systems. How is structural information acquired and maintained? How is cell shape spatially and temporally regulated? In bacteria, the extracellular cell wall (a micrometer-scale 3D polymer network) and the intracellular actin-like (MreB) cytoskeleton are major determinants of cell shape. As a hallmark of microbial life, the cell wall is the most conspicuous macromolecule expanding in concert with cell growth and one of the most prominent targets for antibiotics. Despite decades of study, the mechanism of cell wall morphogenesis remains poorly understood. In rod-shaped bacteria, actin-like MreB proteins assemble into disconnected membrane-associated filamentous structures that move processively around the cell periphery and are thought to control shape by spatiotemporally organizing macromolecular machineries that effect sidewall elongation. However, the ultrastructure of MreB assemblies and the mechanistic details underlying their morphogenetic function remain to be elucidated.
In the core project of our lab, currently funded by an ERC Consolidator Grant and, previously, an ERC Starting Grant. we investigate the mechanistic details underlying cell wall growth and MreB function(s). Research on the bacterial cytoskeleton is important because some mechanisms might be conserved in higher organisms and/or provide evolutionary cues. Conversely, research on the bacteria-specific cell wall is also highly important because it provides potential strategies for the development of antimicrobials at a time when multiple antibiotics resistance has become a major health concern. Our long-term goals are to understand general principles of bacterial cell morphogenesis and to provide mechanistic templates and new reporters for the screening of novel antibiotics.