Jack W. Szostak

My laboratory is interested in the related challenges of understanding the origin of life on the early earth, and constructing synthetic cellular life in the laboratory.  Focusing on artificial life frees us to explore novel chemical systems, but what we learn from these systems helps us to understand possible pathways leading to the origin of life.  Our basic design for a synthetic cell involves the encapsulation of a spontaneously replicating nucleic acid, which acts as the genetic material, within a spontaneously replicating membrane boundary, which provides spatial localization.  We are using chemical synthesis to make nucleic acids with modified nucleobases and sugar-phosphate backbones.  Our goal is generate a nucleic acid system that can replicate accurately and rapidly, without enzymatic assistance.  We have developed a membrane vesicle system that allows for the repeated growth and division of the vesicles, without the involvement of any biochemical machinery. When we combine the nucleic and membrane systems, we can see limited nucleic acid replication within our membrane vesicles.  Once we achieve repeated cycles of replication of the combined system, we expect to see evolutionary forces come into play, leading to the spontaneous emergence of nucleic acid sequences that contribute to the fitness of the artificial cell.  We are now considering the kinds of innovations could most easily arise and confer a selective advantage at the cellular level.    

Subject areas for rotation projects:

1) Explore prebiotic nucleic acid replication using a chemical model system.

2) Explore the biophysics of our replicating vesicles system.