Scialog: Collaborative Teams - 2016
Deconstructing the cell’s mechanical circuits
There are a bewildering variety of chemical processes and mechanical forces at play in a single living cell. While much remains to be learned, progress has been made in determining which molecules within cells trigger specific biochemical reactions. Researchers refer to the components of these biochemical systems as “modules.” Meanwhile, mechanical forces and the molecular signals a cell uses to regulate them remain relatively unexplored.
Now, financed by an innovative Scialog Award, a newly formed research team will attempt discover at least a few mechanical modules by focusing on a specific system of broad interest– cell extrusion in epithelial sheets. (Epithelial tissues line organs, cavities and blood vessels throughout an animal’s body; epithelial cells form sheets by connecting to one another via their lateral membranes.)
The researchers -- Adriana Dawes (Ohio State), Matthew Ferguson (Boise State), Dinah Loerke (U Denver) and Megan Valentine (UCSB) – have each received $50,000 to come together to attempt to modify and study epithelial cell extrusion in Botryllus schlosseri, also known as the star ascidian, golden star tunicate, or sea squirt.
Oddly, this tiny, multi-celled organism, which grows on boat hulls, buoys and other objects submerged in saltwater, is deemed the closest relative to higher mammals among the phyla of invertebrates because it produces tadpole-like larva and has other developmental and morphological similarities with vertebrates. In addition Botryllus’ genome has been completely cataloged.
The researchers seek to develop a modular mechanical model of epithelial cell extrusion in Botryllus through a combination of experimental, analytical, and modeling approaches. Daweshas expertise in mechano-transduction pathway analysis and modeling of cell mechanics; Loerkehas expertise in image data analysis and mechanical modeling of epithelial layers; Fergusonhas expertise in two-photon microscopy, highresolution visualization and nanoscale mechanics; and Valentinehas expertise in Botryllus as well as fluorescence microscopy, microscale force probes and microrheology (a type of viscoelasticity measurement).
Basically, they will add various drugs to the water in which the sea squirts are growing, and then carefully observe and measure minute changes in cell extrusion and form testable theories about the mechanical forces that bring about those changes. If successful, their research will provide a flexible framework for understanding biochemical and mechanical feedback during extrusion, and, for the first time, identify distinct mechanical modules that generate adaptive mechanical behavior in living cells.
Dawes, Ferguson, Loerke and Valentine are among more than 60 early career scientists participating in Scialog: Molecules Come to Life, a three-year program jointly sponsored by Research Corporation for Science Advancement (RCSA) and the Gordon and Betty Moore Foundation. Additional funding has been provided by the Simons Foundation. Scialog supports research, intensive dialog and community building to address scientific challenges of global significance. Within each multi-year initiative, Scialog Fellows collaborate in high-risk discovery research on untested ideas and communicate their progress and form new collaborations in annual conferences.
Molecules Come to Life focuses on such questions as, what are the fundamental principles that make a collection of molecules within a cell produce behaviors that we associate with life? How do molecules combine and dynamically interact to form functional units in cells, and how do cells themselves interact to form more complex lifeforms?
The researchers formed their collaboration at a Scialog conference held earlier this year in Tucson, Arizona. There scientists from diverse fields of biology, physics and chemistry engaged in intensive discussions designed to produce creative ideas for innovative research.
“Scialog aims to encourage collaborations between theorists and experimentalists,” said RCSA Program Director Richard Wiener. “And, we encourage approaches that are driven by theory and coarse-grained modeling, that are testable by experiments.”