Marina Elez Marianne De Paepe Lydia Robert

Our research in brief

The generation of variation in the DNA sequence of genomes is a prerequisite for adaptation, on which the long-term survival of species depends. These variations occur spontaneously and can also be induced by DNA damage. Previous research relying on bulk population measurements has revealed that multiple cellular mechanisms control their occurrences: replication fidelity, repair efficiency, induction of stress responses. Bulk studies have also unveiled that most of that variability is neutral.

Our group seeks to complement this knowledge by addressing the generation of variation and its consequences directly at the single cell level, under dynamically controllable conditions. To do so, we develop new tools that combine genetics, molecular biology, fluorescent microscopy, optogenetics, microfluidics, analysis software and modelling.

Fist, these tools enable us to study cell-to-cell variability in the processes controlling the generation of variability. We focus in particular on the generation of point mutations arising from replication errors. Second, they allow us to we measure directly and quantitatively the impact of antibiotics on the generation of genetic variability.

Third, we use these tools, along with more classical approaches, to investigate phage – bacteria reciprocal modulation of mutation rate and to determine the factors responsible for the high mutation rate of bacteriophages.

Fundings

ANR MUMI (2020-2024) Phage and bacteria reciprocal modulation of mutation rate; M. Elez & M. De Paepe

DIM Elicit (36 months; start date jan 2020)  Integrated single-cell level system for investigating mutations and evolution; L. Robert & M. Elez

ANR PRIMAVERA (36 months; start date march 2020) Profiles of Intestinal Membrane Vesicles and Viruses Associated to IBD; M. De Paepe

ANR JCJC (48 months; start date oct 2019) Transient mutators and evolution of antibiotic resistance; L. Robert

Institut Universitaire de France (60 months; start date oct 2019) Directly Measuring Mutation Rates in Single Living Cells​; M. Elez

Emergences Ville de Paris (48 months; start date nov 2018) Directly Measuring Mutation Rates in Single Living Cells​; M. Elez