Prof. Ades studies how cell envelopes provide a barrier between the cell and its environment, possibly blocking antimicrobial drugs. The cell envelope of Gram-negative bacteria plays an essential role for the bacterial cell by providing a barrier between the cell and the environment, determining its morphology, and maintaining structural integrity. The ability of the cell to respond to challenges to the cell envelope is also of considerable medical importance as it is the target of several classes of antimicrobial drugs. The emergence of multidrug-resistant bacteria is a major medical problem and it is crucial that we increase our understanding of the cellular response to antimicrobials. We are using two approaches to better understand how events in the envelope are communicated to the genetic machinery in the cytoplasm where a response can be generated. The first is to investigate the signaling pathways that control the activity of a transcription factor σE, which responds to cell envelope stress. The second is to identify new envelope-sensing pathways. The goals of this research are to uncover these signaling pathways, to determine how they are integrated into the cellular regulatory network, and to investigate in molecular detail how the interactions among members of a pathway result in signal transduction.