De novo construction and evolvability of Minimal Lifelike Systems

Introduction

The de novo creation of living systems is a long-standing dream of humanity. To realize this dream, we need a clear conceptualization of the goal and the experimental means to put it into practice. We think now, the time is ripe to make a serious attempt.

Conceptual Framework

There is emerging consensus that a minimal living system should have the following features:

• Be out-of-equilibrium and self-sustaining
• Have metabolism
• Include an inheritance system
• Have a boundary to keep the constituents together
• Allow a population of such systems to undergo Darwinian evolution

The aim of this proposal is to develop, for the first time, synthetic chemical systems with all of these features.

Methodology

Due to its very nature, MiniLife stands on two equally strong feet: chemistry and biology. The strongest link between them is autocatalysis, which allows reproduction. Our approach to creating the first artificial chemical living system takes the following steps:

1. Identification of new and development of existing autocatalytic (super)systems that function as chemical (and informational) replicators.
2. Coupling of metabolism with chemical replicators.
3. Coupling of autocatalysis to compartment growth and division.
4. Synthesis of a chemical supersystem comprising all three components (replication, metabolism, and compartmentalization).
5. Demonstrating minimal Darwinian evolution upon subjecting the systems synthesized in steps 1-3 to out-of-equilibrium selection regimes.
6. Approaching a minimal living system by enhancing the evolvability of the triple systems developed in step 4.

Consortium

We have assembled a strong consortium that brings together Principal Investigators (PIs) of previous ERC Advanced Grants in three key areas to be integrated:

• Ashkenasy and Otto bring expertise in synthetic chemical self-replicating systems.
• Griffiths brings expertise on compartmentalization using microfluidics.
• Szathmáry is a leading expert on the theory of replicator evolution and computational modeling.

Conclusion

Success would constitute a landmark achievement in basic science.