Creating and Evolving Communities of Synthetic Self-Replicators (CECS2R)

• Applicant: Dr. Elie Benchimol
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Biological and Biomimetic Chemistry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562620671

Understanding how life emerges from chemical systems is one of the most fascinating current scientific challenges. Building life from synthetic molecules is a promising way of addressing this challenge. Synthetic chemical systems capable of self-replication, metabolism, compartmentalization and even rudimentary forms of Darwinian evolution have been observed. The current limit lies in achieving meaningful Darwinian evolution, which requires enlarging the evolutionary space available to these systems while avoiding the Eigen paradox. The project aims to tackle this by achieving Darwinian evolution on fully synthetic self-replicators communities. Replicators will be made from building blocks featuring two thiols to connect them together by oxidation into disulfide oligomers. The building blocks bear short peptide sequences that assemble into β-sheets. The oligomers undergo supramolecular polymerization into fibers (held together by the β-sheets) which break and replicate exponentially, catalyzing their own formation. While systems composed of one (or in a few instances two) building block(s) have been implemented but lack the diversity required for evolution. The project will combine multiple building blocks thus enhancing the possibility for mutation and evolution in multi-replicator systems. The blocks will be designed such that mutation rates are sufficient for Darwinian evolution to occur, but not too high, so that information contained within replicators can be passed on to subsequent generations. Co-evolution of replicators will be ensured by different “food” niches. Cooperation between replicators will then be implemented by having them collectively mediate a common metabolism (i.e. each replicator catalyzes a different step in the synthesis of their “food”). A selection pressure will be applied by changing the environmental/experimental conditions. In conclusion, these systems constitute an important next step in the de-novo synthesis of life.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professor Dr. Sijbren Otto