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The origin and evolution of archaeal lipid membranes
Lead Supervisor: Claudia Bonfio, Department of Biochemistry

Brief summary
This project aims to identify, for the first time, potentially prebiotic chemical pathways that could have led to ancestral archaeal lipids.  Archaeal lipids were likely one of the main components of the last universal common ancestor’s membrane, implying an ancient and potentially abiotic origin. Yet, prebiotic chemical pathways to archaeal lipids are unknown. Inspired by Nature, yet constrained by prebiotic plausibility and environmental conditions, we will explore the chemistry that led to ancestral archaeal lipids on primordial Earth. This work will, in turn, inform our search for environments conducive to (Archaea-like) lipid synthesis on other potentially habitable planets. planetary crust, seen to increase during Earth’s history due to the presence of complex life.

Importance of the area of research concerned
Lipid membranes are essential for all cells to maintain their integrity and individuality. Lipid membranes are also key in differentiating the domains of life. In Archaea, lipids are made of branched isoprenoid units linked to sn-glycerol-1-phosphate via ether bonds; in Bacteria and Eukarya, lipids are made of linear fatty acids linked to sn-glycerol-3-phosphate via ester bonds. This dichotomy in membrane lipid composition, known as the lipid divide, is hypothesized to have appeared early in the evolutionary timeline. Still, the lipid nature of the last universal common ancestor’s cell membrane and the mechanisms that led to its differentiation in Bacteria and Archaea remain unexplored.

What will the student do?
The student will investigate a range of different substrates and pathways under prebiotically-plausible conditions, including alcohol condensation, aldehyde reductive alkylation and ester photoreduction. The student will design and develop novel synthetic methods to generate libraries of archaeal phospholipids using a combination of solution phase, membrane-templated and dry-state chemistries. The resulting lipids will be purified and characterized, and synthetic methods will be optimized to prepare large-scale lipid libraries. The self-assembly properties of synthetic archaeal lipids and their features will be evaluated by fluorescence spectroscopy, light and electron-microscopy. Additionally, encapsulated prebiotic reactions, such as RNA replication and protometabolic processes, will be investigated to better understand the chemistry of bioinspired systems.  The student will also have the opportunity to test photochemical processes in the lab of Paul Rimmer (Department of Physics), expert in prebiotic photochemistry, and to regularly interact with the group of Buzz Baum (MRC LMB), expert in the biochemistry of Archaea. 

Hargreaves W., Mulvihill S. and Deamer D. - Synthesis of phospholipids and membranes in prebiotic conditions. Nature 266, 78-80 (1977).
Bonfio C., Russell D.A., Green N.J., Mariani A. and Sutherland J.D. - Activation chemistry drives the emergence of functionalised protocells. Chem Sci. 11, 1068810697 (2020).
Lloyd C.T., Iwig D.F., Wang B. et al. - Discovery, structure and mechanism of a tetraether lipid synthase. Nature 609, 197–203 (2022). Releva

Requirements as to the educational background of candidates that would be suitable for the project
Due to the nature of the project an undergraduate degree in chemistry or biochemistry is required.

You can find out about applying for this project on the Leverhulme Centre for Life in the Universe widening participation PhD Studentships page.