Lipid Diversity at the Onset of Life

Introduction

The origin of cell membranes is a major unresolved issue in evolution. Evolutionary biology points to the existence of primitive cells with compositionally diverse membranes that could actively participate in genetic and metabolic processes.

Lipid Diversity Assumption

However, the assumption that such lipid diversity is dependent upon enzymatic chemistry has generated models comprising compositionally minimal membranes (binary or ternary mixtures of short-chain fatty or phosphatidic acids) that passively host genetic or metabolic processes.

Project Overview

LipDive seeks to reconcile biology and chemistry by challenging the critical limiting assumption that lipid diversity cannot be achieved through non-enzymatic, prebiotic chemistries.

Objectives

LipDive will identify prebiotic chemistries that could have given rise to compositionally diverse membranes and show how these support characteristic behaviours necessary for nucleic acid replication and membrane division, the hallmarks of a cell cycle.

Methodology

To achieve this goal, I will harness diversity-oriented prebiotic synthesis to non-enzymatically transform primitive pluripotent lipids into libraries of diverse lipids (WP1). These lipids will be used to build compositionally diverse membranes (WP2) capable of interacting with membrane-editing protoenzymes and ribozymes (WP3). Coupling membrane division and nucleic acid replication will ultimately lead to a primitive cell cycle.

Impact

LipDive will advance the state-of-the-art in the origins-of-life field by probing the emergence, assembly, and evolution of cell membranes, and finally connecting prebiotic chemistry and early biology.

Expected Outcomes

LipDive will lead to:

1. A fundamental understanding of the origins of lipid diversity, including the features now associated with bacterial and archaeal lipids.
2. New strategies based on compositionally diverse membranes to probe, sense, or replicate cellular behaviours.
3. A deep-rooted understanding of the emergence and evolution of cellular processes at the molecular level.