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  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Clinician Researcher
  • Department Manager
  • Full Professor
  • Graduate Student
  • Honorary Professor
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
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Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
01
Sep 2021
Ending Date
31
Aug 2026
Status
Ongoing
Members
6
Structures
10

About

A common phenomenon in most microbial infections is the attenuation of the host’s immediate immune response, allowing for long-term colonization. We and others have shown that many pathogens achieve this by manipulating the epigenetic regulation of the host. Epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence but the control of the accessibility to the DNA sequence. Indeed, we demonstrated that pathogens either release factors that directly targets the host chromatin or hijack its epigenetic machinery, both resulting in alterations of the host epigenome. Our project is based on the hypothesis that inhibiting these phenomena will give an advantage to the host and thus facilitate the elimination of the microbe. Importantly, epigenetic modifications, such as DNA and histone modifications, are reversible and modulate gene expression without changing the DNA sequence. This makes them ideal drug targets. In cancer treatment, epigenetic regulators (enzymes and chromatin-binding proteins) are already validated drug targets, with several molecules approved for clinical use. In the context of infection, drugs targeting chromatin have been explored very little. TheraEPI proposes an innovative strategy to fight antimicrobial resistance (AMR) by chemically targeting epigenetic modifications. Our findings strongly suggest that this could be an innovative therapeutic strategy to counteract bacterial advantages and strengthen the host’s natural defences. By targeting the host, this strategy should also minimize the possibility of resistance emergence.

One of the strengths of the project lies in its interdisciplinarity since it combines expertise in the biology and epigenetics of infection (5 teams), in proteomics (1 team) and in drug design, chemo-informatics and medicinal chemistry of epigenetics (2 teams). We will explore seven pathogens (of the genera Chlamydia, Legionella, Listeria, Pseudomonas, Staphylococcus, Streptococcus and Theileria) as models of infection to identify new, specific epigenetic drug candidates and their targets.

Fundings