Structural Microbiology

The cell cycle is at the heart of all forms of life. Our main objective is to understand the mechanisms of the cell cycle in Mycobacteriales, a suborder of Actinobacteria that includes Mycobacterium tuberculosis, using Corynebacterium glutamicum as a model organism. We employ a mechanistic cell biology approach to study the division and elongation machineries and their spatiotemporal regulation. We are also interested in how the division machinery interacts with DNA remodeling systems to ensure efficient chromosome segregation. Our goal is to obtain direct structural insights into the global architecture of the divisome or its sub-complexes, using integrative structural biology methods.

In parallel, we are developing chemical and imaging tools for cell cycle research and antimicrobial discovery. The cell wall is the target of several anti-tuberculosis antibiotics. We exploit cell morphologies resulting from growth defects to discover chemical compounds targeting essential cell cycle mechanisms. In parallel, we use DNA gyrase as a validated target to study relevant compounds against tuberculosis, both through structural characterization (cryo-EM of complexes) and phenotypic analysis using our model system C. glutamicum.

We are developing an innovative screening and characterization pipeline based on high-content imaging and AI-driven analysis, enabling the discovery of anti-mycobacterial drugs in a non-pathogenic model system, before testing the most promising compounds directly on M. tuberculosis.