VAN MELDEREN's TEAM @CM2
The major focus of the CM2 lab is to study bacterial survival mechanisms from molecules to the cells. We are particularly interested in toxin-antitoxin systems, antibiotic-tolerance and bacterial metabolic regulation. Our long-term ambition is to understand metabolic processes involved in bacterial survival and adaptation. My group together with Garcia-Pino’s team is considered one of the leading laboratories working in the field of toxin-antitoxin systems and has a strong track record in the field of bacterial physiology and molecular microbiology.
At the methodological level, in addition to the classical molecular microbiology and genetics methods, we are developing single cell analyses using microfluidics devices coupled to fluorescence microscopy. Observing cells behaviours and characteristics at the single cell level in real time, and being able to track back cell history allows to study rare phenomenon such as persistence to antibiotics.
Evolution of toxin-antitoxin (TA) systems
Toxin-antitoxin (TA) modules are ubiquitous in the prokaryotic genomes. These systems are organized in operons containing two genes that code for a toxic protein and its cognate antitoxin. Using bioinformatics approaches, we are interesting in deciphering the origin and evolution of these evolutionary successful modules.
Signals activating TA systems and outcomes of activation
The role of TA systems in bacterial physiology is highly debated in the community. We are currently undertaking a systematic approach allowing to determine the conditions for TA systems activation and the outcome of this induction both at the population and single-cell levels.
Novel toxins of TA systems with novel activities
We are interested in discovering novel TA systems with novel toxin activities. Using bioinformatics approaches, we established a catalogue of potential novel toxins. These candidates are being tested in vivo in E. coli and cellular mechanisms targeted by the toxin are studied both in vivo and in vitro in collaboration with the Garcia-Pino’s team.
In vitro persistence to antibiotics
Persistence is the ability of a small subpopulation within a clonal population to survive high doses of bactericidal antibiotics. Molecular mechanisms underlying this phenomenon remain poorly characterized and subject to controversy. Our main goal is to better understand what are the physiological parameters and molecular mechanisms that differentiate persister cells from their antibiotic-sensitive sister cells.