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15 NSFBIO: Excitocell: A rewired eukaryotic cell model for the analysis and design of cellular morphogenesis

Reference	BB/P01190X/1
Principal Investigator / Supervisor	Professor Andrew Goryachev
Co-Investigators / Co-Supervisors
Institution	University of Edinburgh
Department	Sch of Biological Sciences
Funding type	Research
Value (£)	322,160
Status	Completed
Type	Research Grant
Start date	01/11/2017
End date	31/12/2020
Duration	38 months

Abstract

Bilateral BBSRC-NSF/BIO: Excitocell: A rewired eukaryotic cell model for the analysis and design of cellular morphogenesis applies a synthetic approach to investigate cortical excitability. Recently the PIs found that oocytes and embryonic cells in frogs and starfish can support sustained waves of Rho activity and actin assembly. Wave propagation is based on Rho autoactivation and actin-mediated Rho inhibition, and is proposed 1) to explain key features of cytokinetic pattern formation during cell division, and 2) to be generally applicable in animal cells. This collaborative proposal will couple computational modeling of excitable dynamics to live-cell imaging in whole cells and development of a new ex vivo model of cortical dynamics.

Summary

Excitable dynamics is a fundamental example of an emergent behavior in complex systems, which, although observed and studied by various branches of science and engineering, has received little attention in biology outside the context of the nervous system. The excitable dynamics discovered by the PIs represents a readily quantifiable cortical pattern-forming behavior that is potentially controlled by a compact molecular module, and thus amenable to integrated mathematical and experimental study. The PIs propose a novel synthetic biology approach to reconstitute cortical excitability in simplified rewired cells and in an ex vivo system with a high level of experimental control. Adopting this systems and synthetic biology approach, in contrast to top-down genetic analysis, is intended to produce an experimentally-validated model of the core physiological module.

Impact Summary

The project promises to reveal systems properties of the eukaryotic cell cortex that are directly relevant to diverse cell behaviors such as cell division, wound healing, and cell motility. The utility of project products, both experimental results and associated theoretical models, extend well beyond the PIs specific research aims. The results will promote use of synthetic biology approaches and systems biology thinking in cell biology. The project will create and disseminate novel research tools (molecular probes and computer codes) of broad applicability, and will yield images and videos of intrinsic research, pedagogical, and artistic value beyond the specific research aims. This project directly supports training for postdocs and undergraduates, embedded research opportunities for high-school teachers and K12 outreach activities including access for students to working labs and scientists. It supports communication of research in cell and systems biology to the public through exhibits and workshops. A major project component takes place at a marine field station, thus supporting infrastructure and facilitating access by other scientists to marine biological resources.

Committee	Research Committee C (Genes, development and STEM approaches to biology)
Research Topics	Synthetic Biology, Systems Biology
Research Priority	X – Research Priority information not available
Research Initiative	UK BBSRC-US NSF/BIO (NSFBIO) [2014]
Funding Scheme	X – not Funded via a specific Funding Scheme

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