Cells must convert information about the environment into the activity of intracellular effectors, such as transcription factors or metabolic enzymes, in order to generate an appropriate cellular response. A cell “knows” only so much about an external signal as is transmitted through the appropriate signaling pathway to a downstream effector. How signaling pathways are wired to perform appropriate transformations on their input signals and how networks can be tuned on adaptive and evolutionary timescales to adjust these transformations remains an outstanding question. Furthermore, how an effector’s activation carries information and produces an appropriate cellular response is often poorly understood. Information can be encoded in the identity and/or dynamics of an effector. How signaling networks control the dynamics of effector activation and how these dynamics are decoded by promoters to generate distinct gene expression programs is of particular interest. These questions represent critical gaps in our understanding of how healthy and diseased cells respond, or make decisions, in response to stimuli. My research uses Saccharomyces cerevisiae, or budding yeast, as a model organism for addressing these questions in biological signal processing.
Scott, T, Sweeney, K and MN McClean (2019) Biological signal generators: integrating synthetic biology tools and in silico control Current Opinions in Systems Biology 14:58-65
Gasch AP, Yu FB, Hose J, Escalante LE, Place M, Bacher R, Kanbar J, Ciobanu D, Sandor L, Grigoriev IV, Kendziorski C, Quake SR, McClean MN (2017) Single-cell RNA sequencing reveals instrinsic and extrinsic regulatory heterogeneity in yeast responding to stress PLOS Biology 15(12) doi:10.1371/journal.pbio.2004050
Dexter, J.P., Xu, P., Gunawardena, J., and McClean, MN (2015) Robust network structure of the Sln1-Ypd1-Ssk1 three-component phospho-relay prevents unintended activation of the HOG MAPK pathway in Saccharomyces cerevisiae BMC Systems Biology 9:17
Petrenko, N. Chereji, RV., McClean, MN., Morosov, AV., Broach, JR (2013) Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses Mol Biol Cell 24(12) 2045-57