Exobiology and Evolutionary Biology

Replicating Vesicles and the Emergence of Life

PI: Jack Szostak

The goal of the proposed research is to improve our understanding of the origin of life on earth, and of the potential for life to arise on other planets. This proposal is focused on the role of membranes as replicating cellular compartment boundaries. It is a continuation of work currently funded by the NASA Exobiology Program. Our specific goals are:

1. To explore prebiotically realistic pathways for the formation, growth and division of membrane vesicles.

2. To study the permeability properties of model protocell membranes, and the potential roles of pH gradients in energy storage and transformation in early cells.

3. To demonstrate both spontaneous and catalyzed nucleic acid synthesis inside model protocell vesicles.

We will approach these goals using a wide range of methods, beginning with the chemical synthesis of simple lipids. Vesicles prepared with mixtures of fatty acids and their derivatives will be characterized by a variety of biophysical techniques, including light scattering, fluorescence methods and microscopy. Permeability and pH gradient studies will make use primarily of methods based on fluorescent dyes that exhibit ligand or pH sensitive fluorescence. Studies of nucleic acid synthesis will use standard molecular biology methods such as gel electrophoresis to follow the course of the reactions, complemented by mass spectrometry (MALDI-TOF) for product characterization.

The significance of the proposed work lies in its potential to discover surprising and unanticipated phenomena related to the origin of life. For example, our currently funded work led to the finding that clay particles can act to bring together nucleic acids and membrane vesicles, and also led to the discovery of a simple mechanism by which nucleic acid replication could directly influence the growth of the membrane boundary of a primitive cell. The present proposal could go even further in identifying plausible pathways from molecules to cells. A better understanding of the origin of life is central to the stated goals of the Astrobiology and Exobiology Programs of NASA. Moreover, an improved understanding of the conditions under which life could emerge, and of the possible nature of early living systems, will facilitate the search for life (or signs of extinct life) in other solar system environments such as Mars and Europa.