The origin and evolution of archaeal lipids
Lead supervisor: Claudia Bonfio, Department of Biochemistry
Co-supervisors: David A. Russell, Department of Biochemistry
Research proposal
Background and Objectives
Understanding the formation of early cell membranes is key to unravelling the origins of life. Archaea, one of the earliest domains, possess membranes composed of isoprenoid ether lipids, which differ significantly from the fatty acid-based membranes of bacteria and eukaryotes. However, the prebiotic pathways leading to these archaeal lipids and their functional significance in early protocell membranes remain poorly understood.
This project aims to:
1) Identify plausible prebiotic pathways for the formation of ancestral archaeal lipids.
2) Determine the functional properties these lipids could have imparted to primitive membranes.
These objectives can be pursued independently, providing flexibility in the research approach. Over eight weeks, the student will gain hands-on experience in prebiotic lipid chemistry while generating valuable preliminary data for the research group.
Methodology
1. Prebiotic Synthesis of Archaeal Lipid Precursors
The first stage will investigate the reaction of glycerol with isoprenoid alcohols (farnesol, nerolidol) under conditions relevant to the early Earth. Various catalysts, including clay minerals (e.g., kaolinite, montmorillonite) and oxophilic metal salts (e.g., iron, aluminium), will be screened for their role in promoting glycerol ether bond formation. Reaction products will be analysed using:
- Thin Layer Chromatography (TLC) for initial separations,
- High-Performance Liquid Chromatography (HPLC) and Gas Chromatography-Mass Spectrometry (GC-MS) for mixture analysis,
- Nuclear Magnetic Resonance (NMR) Spectroscopy for product characterisation.
2. Functional Analysis of Model Ancestral Archaea Lipids
In parallel, the student will synthesise model archaea-like lipids using established methods within the research group. These will include:
- glycerol monoethers,
- glycerol diethers,
- ether-based phosphatidic acids.
Each lipid will be purified by column chromatography and characterised by NMR. Their ability to self-assemble into membranes will be assessed via critical aggregation concentration (CAC) assays using fluorescent dyes. Further experiments will investigate:
- Lipid packing and ordering via fluorescence polarisation,
- Membrane surface hydrophobicity and charge using electrochemical and spectroscopic assays,
- Compatibility with fatty acid- or bacterial lipid-based membranes to evaluate potential roles in mixed protocell systems.
Training and Supervision
This project provides an excellent introduction to interdisciplinary research, combining organic synthesis with biophysical characterisation. The student will receive training in:
- Lipid synthesis and purification,
- Analytical techniques (chromatography, mass spectrometry, NMR),
- Membrane biophysics, including lipid self-assembly and lipid packing studies.
Additionally, they will develop critical thinking, communication, and data analysis skills, with mentorship from the group leader and senior lab members.
Expertise and Feasibility
The success of this project is supported by:
- My expertise in prebiotic organic and supramolecular chemistry, bridging lipid chemistry and early membrane evolution.
- The interdisciplinary strength of my research group, which integrates organic synthesis with biological and biophysical approaches.
- Preliminary findings, which confirm the feasibility of synthesising archaea-like lipids.
This research will provide the student with valuable laboratory experience while contributing to our understanding of the emergence of archaeal membranes - an essential step in the origins of cellular life.