Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Towards the Design and Synthesis of an Artificial Cell
The complexity of modern biological life has long made it difficult to understand how life could emerge spontaneously from the chemistry of the early earth. The key to resolving this mystery lies in the simplicity of the earliest living cells. Through our efforts to synthesize extremely simple artificial cells, we hope to discover plausible pathways for the transition from chemical evolution to Darwinian evolution. We view the two key components of a primitive cell as a self-replicating nucleic acid genome, and a self-replicating cell membrane. We have recently described a simple and robust pathway for the coupled growth and division of a model primitive cell membrane. Much of our current work is focused on the synthesis of self-replicating nucleic acids, including a series of phosphoramidate nucleic acids. While the rate of template copying by the polymerization of amino-sugar nucleotides can be quite good in such model systems, the fidelity of chemical copying is low. This has led us to explore various nucleobase analogs in search of simple ways to enhance the fidelity of chemical replication. I will discuss recent progress towards the realization of an efficient and accurate system for the chemical replication of an informational polymer. I will also describe ways in which a chemically replicating nucleic acid could lead to evolutionary changes in the membrane composition of a simple protocell, as well as ways in which the evolving cell membrane could enhance nucleic acid replication.
This work was supported by the Howard Hughes Medical Institute, the NSF and NASA.
Jack W. Szostak
Department of Molecular Biology
Massachusetts General Hospital
Boston, MA 02114