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

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

10 25 50
 
Description Fundamental achievements have been obtained in building tools of and methods:
1. A reingineered frog oocyte expressing componenets of excitable networks has been derived
2. Discovery of a novel protein resulted in highly reproducible excitable behavior
3. A method for optogenetic manipulation of the system has been mostly built.
Exploitation Route Once published, these findings will have a significant impact on research of other scientists, worldwide.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology