In the Raivio lab we are interested in understanding how microbial cells sense and adjust to environmental changes. Our model system is the Cpx envelope stress response of the genetically amenable organism Escherichia coli. The CpxA sensor kinase and the CpxR response regulator regulate the Cpx stress response and are members of the two-component regulator family, the largest class of signal transduction proteins in nature. CpxA senses misfolded proteins in the bacterial periplasm and transduces this information to CpxR, which mediates an adaptive response by changing the expression of several hundred genes. We use genetic, molecular biological, biochemical, structural, and whole genome gene expression technology to study the mechanisms used by CpxA to sense misfolded proteins and to understand how the downstream targets of the Cpx response lead to amelioration of stress. Recently, we have shown that one mechanism of Cpx-mediated stress relief involves ridding the envelope of nonessential protein complexes. These include virulence determinants in enteropathogenic E. coli, a major cause of infantile diarrhea. These exciting results suggest that the Cpx response may represent an excellent target for the development of novel therapeutic agents. We expect our work to inform us about how bacteria grow and thrive in the environment, how they cause infections, and how we can engineer them to perform beneficial processes.