The work performed has covered several aspects related to the main scope of RNA-Rep, as summarised in the following outcomes.
- Compartmentalisation and prebiotic activation.
Before the beginning of this fellowship, the ER contributed to the development of a so-called "prebiotic activation chemistry" that can be used to simultaneously activate phosphate and carboxylate groups. This activation chemistry was exploited for the synthesis of prebiotic lipids, as well as for the non-enzymatic polymerisation of RNA and peptides. Therefore, after the beginning of this fellowship, the ER exploited the same chemistry to evaluate its compatibility with a library of prebiotic lipid membranes. Results: Only membranes made of phospholipids bearing a cyclic phosphate headgroup were found to be fully stable and inert to the conditions required for the prebiotic activation of nucleotides and amino acids.
- Membrane-bound biological building blocks.
Fatty acids are considered among the most prebiotic class of lipids likely available on early Earth. Therefore, the ER explored the effect of activation chemistry on membranes made of fatty acids. Results: When membranes made of fatty acids were exposed to activation chemistry, monomeric fatty acids were found to be reactive. The activation of fatty acids' headgroups by prebiotic activating agents yields novel species, namely fatty acylated nucleotides and amino acids. Such amphiphilic species can interact with lipid membranes, driving their growth and co-localising relevant biomolecules (such as RNA strands).
- Compartmentalisation and thermal fluctuations.
Evaluating the effect of thermal fluctuations on lipid membranes was of fundamental importance for the further development of RNA-Rep. Results: While phospholipid-based membranes are stable upon exposure to a wide range of temperatures, membranes made of fatty acids were found to undergo a phase transition to oil droplets upon heating. Such phase transition is reversible and tunable and can be exploited to drive the generation of a new cohort of protocells with reshuffled content.
Overall, all the results obtained with this fellowship validate the proposed approach and pave the way for the efficient multiple cycling of non-enzymatic RNA polymerisation within compartments.
Publications (in the context of RNA-Rep):
Liu Z., Wu L., Xu J., Bonfio C., Russell D. A., Sutherland J. D. - Harnessing chemical energy for the activation and joining of prebiotic building blocks. Nature Chemistry (2020), 12, 1023-1028.
Bonfio C.*, Russell D. A., Green N. J., Mariani A., Sutherland J. D. - Activation chemistry drives the emergence of functionalised protocells. Chemical Science (2020), 11, 10688-10697.
Rubio-Sanchez R., Wang A., O’Flaherty D., Coscia F., Di Michele L., Cicuta P., Bonfio C.* – Thermal oscillations enable reshuffling of genetic material in a primitive cell cycle. BioRxiv (2021), DOI: 10.1101/2021.04.01.438038.
Other publications:
Pellegrini L., Bonfio C., Chadwick J., Begum F., Skehel M., Lancaster M. Choroid plexus organoids predict CNS drug permeability and reveal human CSF proteins produced by specialized cell types. Science (2020), 369, eaaz5626.
Bonfio C.* - The curious case of peptide-coordinated iron-sulfur clusters: prebiotic and biomimetic insights. Dalton Transactions (2021), 50, 801-807.
Dissemination (selected conferences):
Jan 2021 Origin of Life - Early Career Network 1st Symposium (Plenary e-lecture)
Jun 2020 Departmental e-Seminar - Earth Life Science Institute (ELSI), Tokyo, JP
Feb 2020 Dalton Emerging Researcher Award Lecture - University of Bristol, UK
Jan 2020 Meeting of Young Chemists of the Països Catalans - Sitges, ES (Plenary lecture)
Oct 2019 Departmental Seminar - Soft Micro Systems, CNRS, Univ. Bordeaux, FR
Communication and outreach activities:
Sep 2019 Speaker (title of the talk: “A recipe for primordial life”) - European Researchers' Night, Cambridge
Jul 2019 Exhibition Designer and Leading Coordinator (title of the exhibition "A recipe for primordial life") - Royal Society Summer Science Exhibition, London, UK
since 2019 Marie Skłodowska Curie Actions (MSCA) Ambassador - delivered seminars on MSCA project writing at IUPAC 2019 (Paris, FR) and at online events organised by the European Young Chemist Network (2020)
