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.
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.
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.
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
Dünkler A
(2021)
Type V myosin focuses the polarisome and shapes the tip of yeast cells.
in The Journal of cell biology
Goryachev AB
(2019)
Autoactivation of small GTPases by the GEF-effector positive feedback modules.
in F1000Research
Goryachev AB
(2020)
Compete or Coexist? Why the Same Mechanisms of Symmetry Breaking Can Yield Distinct Outcomes.
in Cells
Goryachev AB
(2021)
Symmetry Breaking as an Interdisciplinary Concept Unifying Cell and Developmental Biology.
in Cells
Kita AM
(2019)
Spindle-F-actin interactions in mitotic spindles in an intact vertebrate epithelium.
in Molecular biology of the cell
Landino J
(2021)
Rho and F-actin self-organize within an artificial cell cortex
Landino J
(2021)
Rho and F-actin self-organize within an artificial cell cortex.
in Current biology : CB
Maryshev I
(2019)
Dry active turbulence in a model for microtubule-motor mixtures
in Soft Matter
Maryshev I
(2020)
Pattern formation in active model C with anchoring: bands, aster networks, and foams.
in Soft matter
Maryshev I
(2018)
Kinetic theory of pattern formation in mixtures of microtubules and molecular motors.
in Physical review. E
Michaud A
(2022)
A versatile cortical pattern-forming circuit based on Rho, F-actin, Ect2, and RGA-3/4.
in The Journal of cell biology
Michaud A
(2021)
Cortical excitability and cell division.
in Current biology : CB
Stephenson RE
(2019)
Rho Flares Repair Local Tight Junction Leaks.
in Developmental cell
Van Loon AP
(2020)
Cortical contraction drives the 3D patterning of epithelial cell surfaces.
in The Journal of cell biology
Van Loon AP
(2021)
Stochastic contraction of myosin minifilaments drives evolution of microridge protrusion patterns in epithelial cells.
in Molecular biology of the cell
Varadarajan S
(2022)
Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling
in Journal of Cell Biology
| 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. Research with re-engineered frog oocytes resulted in discovery of totally novel oscillatory behavior on the cell surface. 4. Oscillatory dynamcis and excitable waves have been reconstitited successfully in the frog cell extract on the surface of artificial lipid bilayer 5. A biophysical model of the wave dynamics has been meticulously analysed and quantitative insight into the system behavior extracted |
| Exploitation Route | Once published, these findings will have a significant impact on research of other scientists, worldwide. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | 20-BBSRC/NSF-BIO: Synthetic Control of Pattern Formation and Morphogenesis in a Purposefully Rewired Vertebrate Cell |
| Amount | £400,402 (GBP) |
| Funding ID | BB/W013614/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 12/2025 |
| Description | Leverhulme Trust Award RPG-2020-222 |
| Amount | £176,601 (GBP) |
| Funding ID | RPG-2020-222 |
| Organisation | The Leverhulme Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2021 |
| End | 12/2023 |
| Description | Collaboration with Prof. A. Sagasti |
| Organisation | University of California, Los Angeles (UCLA) |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We analysed the data produced by our partners, developed theoretical model, simulated the model, proposed experiments, wrote the paper |
| Collaborator Contribution | Our partners shared their unpublished data, perfromed proposed by us experiments, wrote the paper |
| Impact | mutidisciplinary: Edinburgh - biophysics, computational modeling; UCLA: cell biology |
| Start Year | 2017 |