Project #6535
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#6535 : Dissecting the peptidoglycan trafficking machinery using gene trap mutagenesis in near-haploid human cells
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Name of Applicant : Christiane Brenner
Date of application : 02-06-2016
Unit : Biology and Genetics of Bacterial Cell Wall
Location : Duclaux/Aile Bertrand RB
Phone : 0140613986
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Project context and summary :

It has been found in the past that the peptidoglycan (PGN) degradation fragments DAP-containing muramyl tripeptide (M-triDAP) and muramyl di-peptide (MDP) stimulate innate immune receptors Nod1 and Nod2. However, it remains to be clarified how the fragments reach Nod1 and Nod2, since these receptors are intracellular. The aim of the project is thus to investigate novel factors in peptidoglycan signalling, using gene trap mutagenesis in human near-haploid cells to randomly knock out genes and do a genome wide screen to establish a library. There is a pressing need to find novel therapeutic strategies, and it has been shown in the past that the above described technique of finding genes works well for this (see Carrette et al., 2011). Results will be validated in relevant mouse models and epithelial cell lines using CRISPR-Cas.

Related team publications :
Link to Pubmed [PMID] – 24746552: The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling
Link to Pubmed [PMID] – 23768497: Penicillin resistance compromises Nod1-dependent proinflammatory activity and virulence fitness of neisseria meningitidis
Link to Pubmed [PMID] – 21471573: Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide
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Project Type : Medium
Status : Closed

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