To investigate how cells measure and interpret signaling inputs, the Kolenbrander Ho lab focuses on a highly-conserved signaling pathway, the ERK pathway, and its role in instructing cell fates at the anterior (future head) and posterior (future tail) of the Drosophila fruit fly embryo. Even though we study this pathway in flies, ERK signaling is highly-conserved. It is important throughout human development and often goes awry in cancer. In the fly embryo, there are two gradients of ERK signaling at the poles that turn on different gene expression programs at the different levels, or thresholds, of signaling. If cells can accurately determine their position within the gradient, then they can take on the right fate. But how do they do this?
Our strategy is to measure signaling in the embryo in the highest detail that we can! This involves building new tools that allow us to see the events of signaling happening in real time, including receptor activation and transcription. We also use optogenetics, a tool that allows us to control protein activity with blue light, to turn on ERK signaling exactly where and when we shine light on the embryo. These tools together give us amazing control to compare signaling inputs and gene expression outputs.
A pYtag biosensor shows endogenous Torso receptor activity in a live embryo
(From Ho, EK et al, 2025)
An MS2/MCP biosensor shows byn transcription in response to optogenetic ERK stimulus. Each bright dot is a burst of transcription from a single nucleus.
(From Ho, EK et al, 2023)