Curated Optogenetic Publication Database

Abstract: The bacterial stress response is an intricately regulated system that plays a critical role in cellular resistance to drug treatment. Stress response genes are organized into networks with transcriptional regulators controlling downstream genes, but how variability in these regulators affects the downstream response remains unclear. We investigate how heterogeneity in the virulence regulator PhoP propagates to its diverse regulon. Using optogenetic control of PhoP expression and information theory, we find that downstream genes differ in mean expression, sensitivity to PhoP levels, and signal transmission reliability. These response functions also vary between individual cells, increasing population heterogeneity. We tie these variations to cell survival upon exposure to a clinically relevant antimicrobial peptide, showing that while high expression of the PhoP-regulon gene pmrD provides protection, cell survival is best determined by the integrated PhoP and pmrD expression levels. Our findings demonstrate that heterogeneous expression of stress response regulators has clear consequences for bacterial stress survival.

Abstract: Cell signaling through direct physical cell–cell contacts plays vital roles in biology during development, angiogenesis, and immune response. Intercellular communication mechanisms between synthetic cells constructed from the bottom up are majorly reliant on diffusible chemical signals, thus limiting the range of responses in receiver cells. Engineering contact-dependent signaling between synthetic cells promises to unlock more complicated signaling schemes with spatial responses. Herein, a light-activated contact-dependent communication scheme for synthetic cells is designed and demonstrated. A split luminescent protein is utilized to limit signal generation exclusively to contact interfaces of synthetic cells, driving the recruitment of a photoswitchable protein in receiver cells, akin to juxtacrine signaling in living cells. The modular design not only demonstrates contact-dependent communication between synthetic cells but also provides a platform for engineering orthogonal contact-dependent signaling mechanisms.