A grand challenge in bottom-up synthetic biology is to design and construct synthetic cells with life-like properties from a minimal number of parts. Achieving this goal would be a major engineering feat and enable an understanding of how living systems work from the perspective of physical chemistry. Towards this, we have exploited bottom-up approaches and generated new insights into the impact of compartmentalization on the thermodynamics and kinetics of incorporated enzyme reactions. Our findings that dynamic coacervation can ignite dormant enzyme reactions provides the conceptual framework for our plan to build sustained out-of-equilibrium synthetic cellular systems. In MinSynCell, the aims are to:
1) Define how molecular reaction networks are tuned by compartmentalization.
2) Build minimal synthetic compartments with self-sustained, out-of-equilibrium behaviour.
3) Utilize communication to coordinate reaction networks within populations of cells.
Together, these objectives test our overarching hypothesis that sustained out-of-equilibrium systems can be established by interconnecting three features: molecular reaction networks, compartmentalization and communication. Key to this endeavour is our unique combination of chemical, biochemical and biophysical tools for quantitative characterization of synthetic cellular systems. We are primed to address the major engineering challenge of building sustained out-of-equilibrium synthetic cellular systems and to tackle a central problem in biological sciences: “How do biological cells and tissues sustain life from collections of non-living molecules?” Our interdisciplinary approach will provide novel tools to the community and represents a unique multidisciplinary approach that will ultimately define the chemico-physical parameters of life. This can lead to unprecedented opportunities to rationally engineer molecular systems which may supersede biological capabilities.
