We are delighted to announce that our Colox project has received funding from the ANR!
We are recruiting two postdoctoral researchers at the Institut Pasteur in Paris.
One of them will be recruited for a period of 36 months to join my group https://research.pasteur.fr/en/team/group-nathalie-sauvonnet/ so please don’t hesitate to send me your application by mail [email protected]!
Here is the sum of our project:
Impact of oxygen on human colonic barrier under physiological and infection conditions
The human colon maintains a steep oxygen (O₂) gradient, shaped by epithelial and microbial metabolism, which is essential for barrier integrity and sustaining an anaerobic microbiota. During infection, this balance is disrupted, causing barrier dysfunction, dysbiosis, pathogen expansion, and immune activation. How O₂ gradient influence epithelial cell fate, mucus properties, and immune responses during infection remains poorly understood. Clostridioides difficile (CD), an anaerobic pathogen, thrives in low O₂ environments and triggers massive neutrophil recruitment, yet the interplay between O2, CD, and host immunity is unresolved.
The ColOx project aims to define the role of O₂ levels in the human colonic barrier under physiological and infectious conditions by challenging the system with CD infection and neutrophils. Project objectives are to determine:
1- Mapping of O2 tensions in human colon-on-chip upon several O₂ tension configurations
2- Impact of O2 variation on the epithelial and mucus layers under physiological condition
3- Impact of O2 gradient on colonic barrier under infection condition using CD as a challenger
4- Impact of hypoxia on the CD and neutrophils interplay
By integrating patient-derived colonic organoids, endothelial and immune cells into organ-on-chip devices exposed to controlled O₂ environments, ColOx enables causal studies of epithelial, microbial, and immune interactions. Using an interdisciplinary approach—including live O₂ mapping, transcriptomic analyses, mucus characterization, CD infection assays, and neutrophil functional studies—ColOx will generate novel insights into how O₂ regulates barrier function and host–microbe dynamics in health and disease.
