Exploring the Origins of Life: From Prebiotic Chemistry to RNA World Dynamics

The seminar will be delivered by Sheref Mansy and Sabine Müller, each bringing unique perspectives to the exploration of life's origins. Together, they will delve into the chemical and molecular processes that may have led to the emergence of self-sustaining systems and the dynamic role of RNA in early life.

Sheref Mansy: To explore the chemical process which lead to the emergence of a self-sustained chemical systems capable of Darwinian evolution, we investigated reactions that produce prebiotically plausible catalysts for metabolism and explored the formation and dynamics of environmentally stable vesicles. Assuming a geological setting consisting of a lake at the surface of the early Earth, we probed the influence of UV light on the stability of small peptides. As we previously reported, UV light leads to the photolysis of cysteine residues, converting these positions to alanine. The released hydrosulfide can then be incorporated into iron-sulfur clusters. We have now investigated the photochemistry further to determine the effect of metal ions on the photostability of prebiotically plausible peptides. We have also determined how solution conditions impact the type of iron-sulfur cluster formed, and have demonstrated the formation of a nitrogenase-like [6Fe-9S] cluster. Finally, we’ll present our model of a growing dividing-protocell.

Sabine Müller: The development of functional RNAs capable of catalysing a variety of chemical reactions has been an important goal for substantiating the RNA world hypothesis. We have designed and studied a number of hairpin ribozyme variants that mediate RNA processing reactions in different scenarios, including recombination, and splicing. Furthermore, we have demonstrated that encapsulation of RNA in vesicles, which is believed to have been a defining feature of the earliest cells, stabilises the active conformation and restores the activity of folding-deficient mutants. More recently, we have shown that neutral networks of the hairpin and hammerhead ribozyme overlap, and that sequences at the intersection of these networks have catalytic functions corresponding to both ribozymes. A single RNA sequence is capable of adopting both the hairpin and hammerhead fold and processing a variety of substrates. Investigating this complex scenario in vesicles is underway. In conjunction with our ribozyme variants for RNA ligation by recombination and RNA splicing, these catalysts not only serve as intriguing models for the activities of the RNA world but also as prospective tools for RNA engineering. For example, they can be employed to generate long RNAs bearing site-specific modifications, as previously demonstrated and currently under re-investigation.