The network of protein quality control factors in the cell envelope of Escherichia coli

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Each cell hosts thousands of different proteins that vary greatly in abundance and chemical properties. To ensure that all proteins are biologically active, localised to the proper cellular compartment and are present in appropriate quantity, efficient mechanisms of quality control were established during evolution. The failure of quality control can influence cell growth (cancer, bacterial pathogenicity) and can cause severe diseases that are based on protein folding, localisation and degradation problems (e.g. Alzheimer¿s and prion diseases, cystic fibrosis, arthritis). It is therefore of general relevance to study the fundamental mechanisms of protein quality control on the molecular level. We propose to use a simple experimental system, the bacterial cell envelope, and an integrated approach comprising genetics, phenotype and metabolomic analyses and in vitro biochemistry, to reveal the basic biological concepts governing protein diagnosis, repair and degradation. In phase 1 of the project, we will identify and characterise pathways of protein folding, repair and degradation by studying the roles and interconnections of the relevant cellular components that is the various chaperones, folding catalysts and proteases.