Jack W. Szostak

Department of Genetics
Department of Molecular Biology
Center for Computational and Integrative Biology
Simches Research Center, CPZN 7250
185 Cambridge St.
Boston, MA 02114
Tel: (617) 726-5981
Fax: (617) 726-6893
Email: szostak@molbio.mgh.harvard.edu
Web Page: The Szostak Lab Page
CCIB Lab Site: http://ccib.mgh.harvard.edu/szostaklab.htm
9 postdoctoral fellows, 8 graduate students

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.

References:

Hanczyc MM, Fujikawa SM, Szostak JW. Experimental Models of Primitive Cellular Compartments: Encapsulation, Growth and Division. Science, 2003; 302:618-622.
Chen IA, Roberts RW and Szostak JW. The Emergence of Competition Between Model Protocells. Science, 2004; 305:1474-1476.
Mansy SS, Schrum JP, Krishnamurthy M, Tobé S, Treco D, and Szostak JW. Template-directed Synthesis of a Genetic Polymer in a Model Protocell. Nature, 2008; 454:122-5.
Zhu TF and Szostak JW. A robust pathway for protocell growth and division under plausible prebiotic conditions. J. Am. Chem. Soc., 2009, 131: 5705–5713.

BBS webpage updated 12/02/2009