I conducted this research in the laboratory of Dr. Sergi Regot. In the Regot Lab, we use biosensors and live-cell imaging to study a wide range of complex biological processes, from embryo development to immune signaling. My recent work seeks to understand innate immunity in the context of the epithelial monolayer, the outermost layer of cells that is often in close proximity to microbes. Epithelial tissues must quantify these microbes in order to maintain a balanced immune state.
To understand how this quantification is achieved, we designed a screen of microbe-related signals and measured the nuclear translocation and transcriptional activation of the master immune regulator —NF-κB — in thousands of single cells. We found that as a population, epithelial cells respond to bacterial molecules by activating fractions of cells in an all-or-nothing (i.e., digital) manner. An epigenetic switch that regulates receptor expression maintains the responding cell fraction. The fraction of responding cells can be increased by prolonged innate immune signaling via cytokines that trigger oscillatory NF-κB activity. Epigenetic variegation of receptor expression in single cells allows for long-term, quantitative flexibility in the upper limit of response in the population. This flexible variability at the single-cell level could contribute to the development of diseases that involve chronic inflammatory states tissues.