Actuality from the project

Research into the droplet Formose reaction has shown that an autocatalytic reaction compartmentalised within growing aqueous droplets can be coupled with the growth of the compartments via diffusion and osmosis. This system already exhibits several properties similar to those of primitive evolving systems: growth, division, variation, competition, rudimentary heredity and selection. A postdoctoral researcher is now exploring a more complex version of this chemistry, notably in the presence of ammonia and prebiotic amines, which effectively stimulate droplet growth (see Lu et al. Nature Chemistry 2025).

In our exploration of the world of RNA, our work has shown that random RNAs reacting in a prebiotic context can form structures of interest for functional RNAs, with molecular steric hindrance playing a key role. Experiments on RNA ligation have also revealed the central role of strand-shifting dynamics in the amplification of information, leading to a detailed scenario for the origin of evolution published in 2025. In parallel, research on RNA–peptide coacervates has progressed towards cycles of selection and regrowth that preserve a proto-genetic identity.

Focus

With regard to the formose reaction, we are investigating the conditions under which multiple inheritable states, robust inheritance, multistability and hysteresis can occur. The next steps involve characterising the non-linear and non-equilibrium dynamics using NMR and LC-MS, followed by testing an alternative compartmentalisation pathway by coupling the formose reaction with the synthesis of primitive amphiphiles capable of spontaneously forming micelles or vesicles that encapsulate the reaction system. On the RNA side, it remains to be demonstrated that information can be amplified through mutual ligation, which, when coupled with selection, would enable a form of primitive evolution.

Relation with others WP

Relation with industries

Syntopia is a spin-off from ESPCI, established in 2025 on the basis of two microfluidics patents, enabling the high-throughput screening of targeted therapies on perfused 3D cell cultures.

www.syntopia.bio

Publication links to the project

Nandan, P., Nghe, P., & Unterberger, J. (2026). Autocatalytic cores in the diluted regime: classification and properties: P. Nandan et al. Journal of Mathematical Biology, 92(3), 36.

https://polytechnique.hal.science/hal-05576876

Lu, H., Blokhuis, A., Turk-MacLeod, R., Karuppusamy, J., Franconi, A., Woronoff, G., … & Griffiths, A. D. (2024). Small-molecule autocatalysis drives compartment growth, competition and reproduction. Nature Chemistry, 16(1), 70-78.

https://universite-paris-saclay.hal.science/hal-04212555

Nghe, P. (2025). A stepwise emergence of evolution in the RNA world. FEBS letters, 599(19), 2706-2717.

https://polytechnique.hal.science/hal-05604203

Calvanese, F., Lambert, C. N., Nghe, P., Zamponi, F., & Weigt, M. (2024). Towards parsimonious generative modeling of RNA families. Nucleic Acids Research, 52(10), 5465-5477.

https://anr.hal.science/hal-05017456v1

Calvanese, F., Peinetti, G., Pavlinova, P., Nghe, P., & Weigt, M. (2025). Integrating experimental feedback improves generative models for biological sequences. Nucleic Acids Research, 53(16), gkaf832.

https://anr.hal.science/hal-05604199v1

Liste des codes développés (avec les liens vers un dépôt publique) et des brevets issus du projet.

2025 N°PCT/EP2026/058430, NEW MICROFLUIDIC DEVICE AND METHOD FOR ITS MANUFACTURE