Jack W. Szostak

About

Jack W. Szostak is a University Professor in the Department of Chemistry at The University of Chicago, with research interests spanning chemical biology, biophysics, organic chemistry, and physical chemistry. His work primarily focuses on understanding the origins of life, particularly how life could have emerged spontaneously from early Earth chemistry. Szostak's research involves synthesizing simple artificial cells to uncover plausible pathways for the transition from chemical evolution to Darwinian evolution, emphasizing the roles of self-replicating nucleic acid genomes and boundary structures such as primitive cell membranes. His laboratory has made significant progress in the synthesis of self-replicating nucleic acids, the coupled growth and division of primitive cell membranes, and investigating routes for the emergence of coded peptide synthesis from the RNA World. Szostak's work also explores model systems that could lead to artificial life with biochemistries different from those of existing biology, including the development of models like the Virtual Circular Genome for primordial RNA replication. His contributions extend to understanding nonenzymatic RNA replication, the formation and stability of protocells, and the potential roles of aminoacylated RNAs in early peptide synthesis. Szostak's extensive career includes positions at Harvard Medical School, Massachusetts General Hospital, and McGill University, along with numerous awards and honors, including the…

Research topics

• Chemistry
• Biology
• Biochemistry
• Computational biology
• Genetics

Selected publications

• Template‐Directed Copying of RNA by Non‐enzymatic Ligation

  Angewandte Chemie International Edition · 2020-06-18 · 81 citations

  articleOpen accessSenior authorCorresponding

  Abstract The non‐enzymatic replication of the primordial genetic material is thought to have enabled the evolution of early forms of RNA‐based life. However, the replication of oligonucleotides long enough to encode catalytic functions is problematic due to the low efficiency of template copying with mononucleotides. We show that template‐directed ligation can assemble long RNAs from shorter oligonucleotides, which would be easier to replicate. The rate of ligation can be greatly enhanced by emp…

  PublisherDOI

• Bulk Self-Assembly of Giant, Unilamellar Vesicles

  ACS Nano · 2020-06-30 · 70 citations

  articleOpen accessCorresponding

  The desire to create cell-like models for fundamental science and applications has spurred extensive effort toward creating giant unilamellar vesicles (GUVs). However, a route to selectively self-assemble GUVs in bulk has remained elusive. In bulk solution, membrane-forming molecules such as phospholipids, single-tailed surfactants, and block copolymers typically self-assemble into multilamellar, onion-like structures. So although self-assembly processes can form nanoscale unilamellar vesicles,…

  PublisherOA PDFDOI

• Simple Lipids Form Stable Higher-Order Structures in Concentrated Sulfuric Acid

  Astrobiology · 2025-03-31 · 8 citations

  articleOpen access

  Venus has become a target of astrobiological interest because it is physically accessible to direct exploration, unlike exoplanets. So far this interest has been motivated not by the explicit expectation of finding life but rather by a desire to understand the limits of biology. The venusian surface is sterilizing, but the cloud deck includes regions with temperatures and pressures conventionally considered compatible with life. However, the venusian clouds are thought to consist of concentrated…

  PublisherDOI

• Nonenzymatic RNA copying with a potentially primordial genetic alphabet

  Proceedings of the National Academy of Sciences · 2025-05-21 · 4 citations

  articleOpen accessSenior author

  Nonenzymatic RNA copying is thought to have been responsible for the replication of genetic information during the origin of life. However, chemical copying with the canonical nucleotides (A, U, G, and C) strongly favors the incorporation of G and C and disfavors the incorporation of A and especially U because of the stronger G:C vs. A:U base pair and the weaker stacking interactions of U. Recent advances in prebiotic chemistry suggest that the 2-thiopyrimidines were precursors to the canonical…

  PublisherDOI

• Efficient Assembly of Functional RNA by <i>in Situ</i> Phosphate Activation and Loop-Closing Ligation

  Journal of the American Chemical Society · 2025-10-20 · 3 citations

  articleOpen accessSenior authorCorresponding

  How ribozymes might have emerged prior to the evolution of an efficient RNA replicase remains an open question. A potential solution involves the nonenzymatic ligation of RNA oligomers that are short enough to have been replicated by nonenzymatic chemistry. However, the high concentrations of metal ions that facilitate ligation are incompatible with primitive protocells. In addition, the mode of oligoribonucleotide 5′-phosphate activation is unclear, and in an aqueous environment the competing h…

  PublisherDOI

Recent grants

• NIH Grant R01GM053936

  NIH · $2.0M · 2005

• Darwinian Chemical Systems

  NSF · $1.5M · 2004–2007

• Nonenzymatic RNA Replication

  NSF · $1.0M · 2021–2023

Frequent coauthors

• Lijun Zhou

  University of Pennsylvania

  206 shared

• Albert C. Fahrenbach

  UNSW Sydney

  170 shared

• Chun Pong Tam

  Howard Hughes Medical Institute

  143 shared

• Dian Ding

  Massachusetts General Hospital

  142 shared

• Derek K. O’Flaherty

  University of Guelph

  138 shared

• Wen Zhang

  Xi’an University

  106 shared

• Victor S. Lelyveld

  Massachusetts General Hospital

  95 shared

• Stephanie J. Zhang

  94 shared

Awards & honors

• Imbach-Townsend Award, IS3NA 2020
• Dewey-Kelley Award, Dept. of Chemistry, University of Nebras…
• Fellow of the Royal Society 2019
• Walker Prize, Museum of Science, Boston MA 2019
• Westheimer Prize, Dept. of Chemistry and Chemical Biology, H…

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