Description du projet
Dévoiler les mécanismes de l’immunité des bactériophages
Les bactériophages sont des virus qui infectent les bactéries. Dans la mesure où les bactéries sont capables de mécanismes immunitaires pour résister à l’infection aux bactériophages, ceux-ci peuvent mettre en œuvre des mécanismes visant à contrer cette résistance. Il s’agit d’une sorte de course à l’armement évolutionnaire. Le projet DEFEND, financé par le CER, entend développer des stratégies thérapeutiques efficaces pour traiter les agents pathogènes résistants aux antibiotiques basés sur les bactériophages. Il compte étudier comment les systèmes immunitaires adaptatifs (CRISPR) et innés protègent les bactéries des virus bactériens (phages) aux niveaux moléculaire, cellulaire et populationnel.
Objectif
Microbes are engaged in an evolutionary arms-race with their viruses and have evolved a spectrum of adaptive and innate defense systems to limit viral predation. Mechanistic insights into defense systems have yielded truly revolutionary genetic tools ranging from CRISPR-based genome editing nucleases to restriction enzymes used for molecular cloning. Despite the ongoing effort to understand defense systems, many antiviral defense systems remain virtually unstudied in and outside their native microbial context, creating huge potential for scientific breakthroughs and development of further game changing applications.
In the timely research proposed here I aim to uncover how adaptive (CRISPR) and innate immune systems protect bacteria from bacterial viruses (phages) at the molecular, cellular and population level. Based on our exiting unpublished observation that extremely phage resistant pathogens in our bacterial strain collection are true collectors of defense systems, I propose to investigate the contribution of each defense system and cooperativity between defense systems for broad and specific bacteriophage resistance. I furthermore aim to determine the molecular mechanism of a dominant set of related innate immune systems found in clinical pathogens, and to reveal how individual phages achieve immune evasion.
To accomplish my goals, I plan to use an interdisciplinary approach combining state-of-the-art molecular microbiology and biophysics at the single molecule and single cell level, with bioinformatics and high-throughput synthetic genomics screens. The project may lead to fundamentally new insights into the mechanism and evolution of virus immunity and will further explore the genetic treasure trove at the interface of virus and host interactions. Our findings will have implications for controlling virus resistance, and will be vital to develop effective therapeutic strategies to treat antibiotic resistant pathogens based on bacteriophages.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
2628 CN Delft
Pays-Bas