RP15

Effect of cell wall modification on the interaction with the host.

For this research project, Mr Krzysztof REGULSKI has been recruited.

Main supervisor

INRA (M. P. Chapot-Chartier)

Co-supervisor

University of Debrecen (E. Rajnavolgi).
Foreseen mobility conditioned to the acceptance of a bi-lateral collaboration project.

Duration : 36 months 

Start date : end of 2008/beginning of 2009

Type of recruitment: This PhD project will be financed by INRA, no eligibility rule.

Objective. To study the influence of peptidoglycan metabolism on the ability of bacterial strains to modulate gut epithelial and dendritic cell responses.

Approach. Mutants of Lactobacillus casei modified in their peptidoglycan structure and/or peptidoglycan hydrolase content will be constructed and characterized for their autolytic properties in vitro. The constructed bacteria and/or their cell wall extracts will be compared in vitro by their ability to activate signalling pathways in epithelial cells and dendritic cell subsets by monitoring cytokine production (multiplex assays) and the expression level of selected genes (QRT-PCR) involved in signalling through membrane (TLR) and cytosolic (NLR, ds RNA binding molecules) molecular sensors.

Expected impact and connections: This project will increase our knowledge on the nature of MAMPs in non pathogenic bacteria and their effects on epithelial and dendritic cell cross talk. Connection to project 9 of CROSS-TALK.

Deliverables.

  • Month-X, construction of cell wall mutants of a selected commensal/probiotic strain.
  • M-Y, identification of cell wall fractions able to activate epithelial or dendritic cells.
  • M-Z, identification of cell signalling pathways activated by bacteria in epithelial or dendritic cells in relation to cell wall component modifications.