Claudia Bonfio
Origins of Life and the Design of Functional Primitive Cells
Research Summary
Our lab investigates how life first emerged from chemistry, focusing on how primitive cells could have formed in the absence of complex biochemical machinery. We explore how early Earth chemistry may have given rise to simple, functional compartments – such as lipid membranes and membraneless coacervates – that organised and supported key biochemical processes.
A central theme of our research is the non-enzymatic diversification of lipids. We challenge the idea that complex cell membranes only appeared after the evolution of lipid-synthesising enzymes. Instead, we investigate how diverse lipids can form spontaneously under prebiotic conditions, creating membranes with rich phase behaviour and dynamic properties. These primitive membranes may have supported essential functions such as RNA replication, molecular encapsulation, and membrane fusion or division.
In parallel, we study coacervates – phase-separated droplets formed from simple peptides and nucleic acids – which provide an alternative model of early compartmentalisation. These droplets can stabilise nucleic acids, enhance their chemical reactivity, and serve as microenvironments for primitive biochemical reactions.
By combining prebiotic chemistry, membrane biophysics, and systems biochemistry, we aim to uncover the physical and chemical principles that shaped the first cells. Our work bridges fundamental questions in the origins of life with broader goals in synthetic biology and biomimetic design.
Research Objectives
- To understand how diverse lipid structures could have emerged from simple prebiotic molecules.
- To investigate how compositionally complex, enzyme-free membranes behave, evolve, and support key biochemical functions.
- To explore the functional roles of membrane-bound and membraneless compartments (e.g., lipid vesicles and coacervates) in organising and enhancing prebiotic chemistry.
- To study how primitive compartments interacted with protoenzymes – short, catalytic peptides – and how such systems could drive dynamic behaviours like fusion, division, and molecular sorting.
- To reconstruct plausible pathways from molecular self-assembly to the first functional protocells by integrating insights from chemistry, biophysics, and evolutionary biology.
Publications
1. Nakashima, K.K. et al. (2025) Compositional and functional diversity of minimal primitive coacervates in a nucleic acid-peptide world [Preprint]. doi:10.26434/chemrxiv-2024-l40ch-v2.
2. Thaipurayil Madanan, K. et al. (2024) ‘Mg2+-driven selection of natural phosphatidic acids in primitive membranes’, Chemical Science, 15(47), pp. 19787–19794. doi:10.1039/d4sc05362a.
3. Aleksandrova, M. et al. (2023) ‘Ring opening of glycerol cyclic phosphates leads to a diverse array of potentially prebiotic phospholipids’, Journal of the American Chemical Society, 145(47), pp. 25614–25620. doi:10.1021/jacs.3c07319.