About MuSE

Mutations, i.e. changes in the genetic sequence of organisms, are the driving force of evolution. They also have important consequences for human health. Our fight against infectious diseases is underpinned by an evolutionary arms race with pathogens, in which mutations fuel the evolution of virulence, antibiotic resistance and bacteriophage escape.

Mutations have been intensively studied for more than a century, shedding light on the mechanisms underlying their production and their effects on individuals and populations. Our group contributes to this body of knowledge by addressing some of the unexplored questions about mutagenesis in phages and bacteria. Some of these require the development of new experimental approaches. Notably, in 2018, we developed a novel, single-cell level approach that combines microscopy, microfluidics, and a fluorescent reporter of replication errors allowing us to follow mutations and their effects directly in single bacteria.

Researcher working on experiment while wearing a lab coat in the MuSE Lab.

Close-up photos of test tubes labeled and arranged in the MuSE Lab.

Portrait of Marina Elez speaking to a colleague in the MuSE Lab

Portrait of Lydia Robert working with a colleague in the MuSE Lab

Petri dishes stacked and ready for analysis in the MuSE Lab

Lab coat hanging over a chair in the MuSE Lab

Close-up photo of pipettes marked and ready for use in the MuSE Lab.

Portrait of Yuvaraj Bhoobalan discussing results with a colleague in the MuSE Lab.

Close-up photo of researcher operating microscope joystick in the MuSE Lab

Images taken in our lab © AiR&D, Alexandre Darmon

Our novel single cell approach to study mutagenesis and evolution

Microfluidic Mutation Accumulation experiment:

Thousands of Escherichia coli cells are grown in the mother machine microfluidic chip and accumulate mutations for hundreds of generations.

Mutation visualization experiment:

Escherichia coli mutH- cells (red) are grown in the mother machine microfluidic chip. Yellow spots mark nascent mutations.

Current projects

Research leads: Lydia ROBERT & Marina ELEZ

Many spontaneous mutations are due to DNA replication errors. Such errors can be repaired by a dedicated system called Mismatch Repair (MMR). Therefore, mutations occur in two steps: the production of an erroneous DNA sequence by the polymerase, and the failure of its repair by MMR.

Recently, we have used our mutation visualization approach to investigate the dynamics of error production, i.e. the first step of mutation occurrence, revealing moderate cell-to-cell variations in error rate during normal growth. Now, we extend our method to visualize simultaneously replication error production and repair by MMR. The second step (i.e. fluctuations of error repair efficiency and the dynamics of mutations caused by repair failures) allows us to fully characterize the mutation dynamics in growing cells.

Four images showing a florescent microscope, a diagram of a microfluidic channel, bacteria growing in the channel and mutations of the bacteria with markers.

Research leads: Marina ELEZ & Marianne DE PAEPE

In this project, we address questions related to the occurrence of mutations during phage infections. Why do DNA phages, even those that use the replication machinery of their hosts, have a mutation rate about two orders of magnitude higher than that of their hosts? Can we modulate the mutation rate of phages? Can we slow down the diversification and evolution of phages? What is the impact of infection on the host mutation rate?

To investigate these questions, we use E. coli and several of its bacteriophages, such as lambda, T4, and M13, as model systems. We address these questions using, in addition to video microscopy and the microfluidics-based mutation visualization experiment originally developed in the group, molecular biology, microbiology, genetics, and genome-wide approaches such as Duplex Sequencing and Chip-Seq.

Our lab is a member of the French Phages Network

Series of three photos taken under a microscope during an experiment showing mutations of cells marked in yellow over time.

Research leads: Marina ELEZ & Lydia ROBERT, recipient of the IMPULSCIENCE Award 2022

Data accumulated over the last decades suggest that under stressful conditions, some cells could trigger specific molecular mechanisms that increase their mutation rate. In particular, bacteria could increase their mutation rate in presence of sublethal concentrations of antibiotics. Traces of antibiotics are often found in natural environments and could increase the rate of adaptation of bacteria and thus their capacity to acquire mutations conferring antibiotic resistance.

Previous studies investigating the effect of stress on mutagenesis were hampered by the limitations of classical experimental approaches. Therefore, we use our new approach to characterize mutagenesis in E.coli in stressful environments. We will visualize replication errors, assessing replication fidelity and repair capacity at the single cell level, and we will also develop a new method to estimate the rate, spectrum and localization of all types of mutations.

Photo taken under a microscope from experiment showing E. coli cells (in red) grown in a microfluidics machine with mutations marked in green on a black background.

Research lead: Marianne DE PAEPE

Changes in the intestinal microbial environment may come with drastic consequences for human’s health. Crohn’s disease (CD) is characterized by chronic inflammation coupled to an imbalance in the composition of the intestinal microbiota (i.e. dysbiosis), as repeatedly pointed out by several teams. Yet, the proximal causes of this dysbiosis are far from being understood. While much is being done towards understanding the role of the gut bacterial components, the biological nanofraction – comprised of viruses and membrane vesicles – remains largely understudied despite being the most abundant. Viruses that infect bacteria, or bacteriophages (phages) play a key role in microbial ecology by modulating bacterial communities as well as playing a role in dysbiosis. Due to their small size, phages and membrane vesicles could also have direct interactions with the intestinal epithelium thus driving inflammation.

Our hypotheses is therefore that there might be a correlation between the abundance and diversity of the intestinal nanofraction and the gut inflammatory state. In collaboration with L. De Sordi (Centre de Recherche Saint-Antoine, Paris), and M. Petit (Micalis, INRAE), we study this quantitatively and qualitatively, thanks to a wide range of techniques from epifluorescence microscopy to metaproteomics and metagenomics, and the nanofraction of intestinal samples of CD patients and healthy volunteers.

This project not only informs understanding of the intestinal nanofraction characterising the physiopathology of CD, but will also set research standards towards profiling the biological nanofraction of multiple human ecosystems and diagnosing disorders.