De novo construction and evolvability of Minimal Lifelike Systems

ongoing

The de novo creation of living systems is a long-standing dream of humanity. To realise this dream, we need a clear conceptualisation of the goal and the experimental means to put it to practice. We think now, time is ripe to make a serious attempt. There is emerging consensus that a minimal living system should be out-of-equilibrium and self-sustaining, have metabolism, an inheritance system, a boundary to keep the constituents together and that a population of such systems should be able to undergo Darwinian evolution. The aim of this proposal is to develop, for the first time, synthetic chemical systems with all of these features. Due to its very nature MiniLife is standing 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 compartmentalisation). (5) Demonstrating minimal Darwinian evolution upon subjecting the systems synthesized in 1-3 to out-of-equilibrium selection regimes. (6) Approaching a minimal living system by enhancing of the evolvability of the triple systems developed in 4. We have assembled a strong consortium that brings together 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 compartmentalisation using microfluidics, and Szathmáry is a leading expert on theory of replicator evolution and computational modelling. Success would constitute a landmark achievement in basic science.