Description du projet
Dynamique des protéines sous-jacentes à la division cellulaire bactérienne
Compte tenu de la prévalence croissante de la résistance aux antibiotiques, une meilleure compréhension du mécanisme de croissance et de division des cellules bactériennes est essentielle au développement de nouveaux antibiotiques efficaces. Cependant, l’étude de la dynamique des protéines dans des cellules bactériennes vivantes s’avère complexe. Financé par le Conseil européen de la recherche, le projet SELFORGANICELL entend étudier la division cellulaire bactérienne à l’aide d’une approche de biologie synthétique. La recherche se concentrera sur l’organisation spatiale et temporelle des protéines de la division cellulaire, et s’appuiera sur la biochimie des protéines et sur des techniques de microscopie à haute résolution pour déchiffrer le réseau biochimique qui sous-tend la division cellulaire. Les résultats du projet amélioreront notre compréhension des systèmes biochimiques complexes qui donnent naissance aux cellules vivantes.
Objectif
One of the most remarkable features of biological systems is their ability to self-organize in space and time. Even a relatively simple cell like the bacterium Escherichia coli has a precisely regulated cellular anatomy, which emerges from dynamic interactions between proteins and the cell membrane. Self-organization allows the cell to perform extremely challenging tasks. For example, for cell division, more than ten different proteins assemble into a complex, yet highly dynamic machine, which controls the invagination of the cell while constantly remodeling itself. Although the individual components involved have been largely identified, how they act together to accomplish this challenge is not understood. It has become clear that sophisticated biochemical networks give rise to intracellular organization, but we have yet to uncover the underlying mechanistic principles.
In this research proposal, I aim to develop a detailed mechanistic understanding of the self-organizing, emergent properties of the cell. To this end, my research group will develop novel in vitro reconstitution experiments combined with high-resolution fluorescence microscopy and theoretical modeling. Following this “bottom-up” approach, we will quantitatively analyze collective protein dynamics and emergent mechanochemical properties of the bacterial cell division machinery. I aim to answer the following fundamental questions:
1) What is the biochemical network giving rise to the dynamic assembly of the divisome?
2) How do the components of the divisome interact to generate force?
3) How do peptidoglycan synthases build the cell wall?
By comparing protein dynamics in vitro with those measured in vivo, we will provide a link between molecular properties and the processes found in the living cell. This project will not only improve our understanding of the bacterial cell, but also open new research avenues for eukaryotic cell biology, synthetic biology and biophysics.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesmathematicspure mathematicsmathematical analysiscomplex analysis
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
3400 Klosterneuburg
Autriche