Adam D. Coster, PhD.
The University of Texas Southwestern Medical Center at Dallas, 2014
How cells integrate external cues in order to make behavioral decisions is a central problem of cell biology. In development and in tissue-homeostasis, cell-fate decisions are made by the integration of multiple morphogenic signals, but how cells convert such combinations of signals into distinct behaviors is not well understood. A major complication is our incomplete knowledge of which signal properties encode the information that cells use for decision-making. A further complication is that the static networks we use to describe cellular signaling pathways are likely to be overly-complex; the true signaling network, in a given cellular context and at a particular point in time, may be much simpler. Using a rigorous and quantitative single-cell imaging approach, I find that such simplicity is present in the integration between Wnt and Transforming Growth Factor Beta (TGFB), which are key developmental pathways. Surprisingly, this insulation extends to the integration of signals within the TGFB superfamily, which are expected to compete for shared components and so interfere with one another during signal transduction. My results thus add clarity to and simplify our understanding of how cells integrate information from the Wnt and TGFB pathways, and further suggest that insulation of signal transduction may be a common feature of morphogenic pathways.
- Coster AD, Thorne CA, Wu LF, Altschuler SJ. Examining Crosstalk among Transforming Growth Factor β, Bone Morphogenetic Protein, and Wnt Pathways. J Biol Chem. 2017;292(1):244‐250. doi:10.1074/jbc.M116.759654
- Coster AD, Wichaidit C, Rajaram S, Altschuler SJ, Wu LF. A simple image correction method for high-throughput microscopy. Nat Methods. 2014;11(6):602. doi:10.1038/nmeth.2971
- Kang J, Hsu CH, Wu Q, et al. Improving drug discovery with high-content phenotypic screens by systematic selection of reporter cell lines. Nat Biotechnol. 2016;34(1):70‐77. doi:10.1038/nbt.3419
This dissertation is permanently electronically archived by UT Southwestern via the URI https://hdl.handle.net/2152.5/3586. That's probably the appropriate reference for the final dissertation contents.
This repo contains all the raw data, images, plots, and code used to write my dissertation back in 2014. Unless specified somewhere in the text or comments, I am the author of all included files.
Feel free to use this content however you please! I've been out of the field for years, so it's extremely unlikely I'll be able to answer any questions about my dissertation, the included files, or the subject matter.