Project

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.