Investigating viral and bacterial dysbiosis through DNA collisions

Investigating viral and bacterial dysbiosis through DNA collisions

By In PhD proposals 2018 On April 4, 2018

Project: Investigating viral and bacterial dysbiosis through DNA collisions

Laboratory: Group Interactions Bacteriophages Bacteria in Animals

Affiliation: BMGE Unit, Institut Pasteur
Address: 25 Rue du Dr. Roux, 75015 Paris

LAB Director
Name: Patrick FORTERRE
Phone number: 0145688830

Name: Laurent DEBARBIEUX
Phone number: 0144389203

Subject Keywords: Virus-host interaction, murine controlled microbiota, metagenomics, intestinal dysbiosis, contact genomics
Summary of lab’s interests: Our team is specialized in the study of bacteriophages infecting bacteria in complex environments such as the gut of mammals. How phages regulate bacterial populations, what are the ecological and evolutionary consequences of phage predation on bacterial populations and consequently on the animal host, are key questions that we address using tools ranging from molecular biology, genetics, genomics and animal models. The lab of co-supervisor (R. Koszul) is specialized in the study of chromosome dynamics in microorganisms. Organizational changes experienced by chromosomes during replication and cell cycle are studied using genome-wide, single-cell technologies and metagenomics.
Project summary: Human gut microbiota is linked to health and its major component is often reduced to bacteria while bacteriophages, viruses infecting bacteria, are equally abundant but understudied. Recent publications have highlighted associations between phage dysbiosis and few diseases but due to major technical hurdles these data remains exclusively observational.
Taking advantage of a new model of controlled microbiota (12 bacterial strains representing the major bacterial species found in mice gut) we aim to develop a process to study the direct interactions between phage and bacteria by applying a metagenomics approach based on DNA contacts (Meta3C). Computational tools will be developed to capture the metabolic activities of prophages in this controlled system over time. Then, several modulations (phage predation, inflammation, infection, antibiotics) of this controlled system will be investigated to implement computational tools, with the aim to anticipate the analysis of more complex human gut samples to reach an unprecedented comprehensive level of the dynamics of phages and bacteria in the gut. Analysis of clinical samples is scheduled during the 3rd year. We envision that our approach will lead to detect, via phage dynamics, early events of bacterial dysbiosis and could therefore be used as a diagnostics tool.
Interdisciplinary aspect of the project: This project requires the intricate collaboration between two teams that have no overlapping expertise but share the same interest in deciphering the genomic network between cells and viruses. The PhD candidate will be trained by specific members of both teams in microbiological routine technics including phage and animal handling as well as genomics, sequencing and computational tools. The candidate will therefore receive an intensive interdisciplinary training along the PhD. In addition, both teams have ongoing national and international collaborations, which will increase the candidate’s exposure to more specific topics such as neural network, genetic engineering or intestinal metabolic functions.
Funding: Ongoing application to Inception program