We are interested in understanding how dynamic molecular interactions are regulated in time and in space to form functional machineries that establish long-range orders and cellular functions in bacteria, with a particular focus on the bacterial cytoskeleton and on the cell envelope, at the frontline of environmental and host-pathogen interactions.
To this end, we combine cutting-edge high-resolution fluorescence microscopy and spectroscopy techniques with powerful genetic, biophysical, biochemical and systems biology approaches to determine mechanistic details underlying cellular and developmental functions in bacteria. We study in particular (but not only) the rod-shaped Gram-positive model bacterium Bacillus subtilis and the Gram-negative ESKAPE pathogen Pseudomonas aeruginosa (classed by the World Health Organization (WHO) as priority 1 (critical) pathogen for R&D in antimicrobial research). Our current work follows 3 main research axes:
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 most prominent target for antibiotics) and the intracellular actin-like (MreB) cytoskeleton are major determinants of cell shape. We and others previously showed that MreB proteins assemble into membrane-associated nanofilaments that move processively around the cell periphery and control shape by organizing and orienting transmembrane enzymes that effect sidewall elongation in the extracellular space. The properties of MreB assemblies, the mechanistic details underlying their morphogenetic function and the interplay between MreB, the plasma membrane and the cell wall synthesizing machineries remain however to be elucidated.
In the core project of our lab, currently funded by an ERC Consolidator Grant, and previously by an ERC Starting Grant, we investigate the mechanistic details underlying cell wall growth, membrane organization and MreB function(s) using a combination of in vivo and in vitro approaches. Research on the bacterial actins 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 bacterial actins to provide mechanistic templates and new reporters for the screening of novel antibiotics.
We are also exploring the cell biology of cellular processes occurring across the bacterial cell wall and/or requiring cell wall remodeling. Currently, these include phage infection, genetic competence and sporulation. These are in general collaborative projects mainly funded by the ANR (French National Research Agency).
We investigate the mode of action of antibiotics targeting the cell envelope in both B. subtilis and the ESKAPE, WHO priority 1 pathogen P. aeruginosa.
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