Group Leader

John Sutherland

Chemical origins of molecular biology

John Sutherland
Group Members
  • Charles-Henri Buffet
  • Kirill Lobodin
  • Bruno Marinic
  • Dougal Ritson
  • Joel Rogers
  • Lucia Trevisan
  • Jianfeng Xu

A true understanding of biology must include knowledge of its chemical origins, and comprehending the chemical events that gave biology its foundations – cellular format, the central dogma, the genetic code – is therefore a fundamental aspect of natural science. Furthermore, understanding the way in which extant biology arose can inform the design of ‘synthetic’ biologies.

We are interested in uncovering prebiotically plausible syntheses of the informational, catalytic and compartment-forming molecules necessary for the emergence of life. We have previously demonstrated the constitutional self-assembly of pyrimidine ribonucleotides from mixtures of simple building blocks, and we are now exploring similar ‘systems chemistry’ approaches to the purine ribonucleotides and ways of assembling RNA from these ribonucleotides with regiocontrol of the internucleotide phosphodiester linkage. We are also interested in the chemical origins of genetically encoded translation and the abiogenesis of lipids.

Overcoming dogma in prebiotic nucleotide synthesis. Previously assumed routes to nucleotides (blue) envisioned the conjoining of preformed nucleobases and ribose. The failure of this ribosylation chemistry (red cross) prompted us to explore other routes resulting in the discovery of a successful synthesis (green) from the same feedstock molecules.
Overcoming dogma in prebiotic nucleotide synthesis.

Selected Publications

Triplet-Encoded Prebiotic RNA Aminoacylation.Su M, Schmitt C, Liu Z, Roberts SJ, Liu KC, Röder K, Jäschke A, Wales DJ, Sutherland JDJ Am Chem Soc 145(29): 15971-15980 (2023)
A Light-Releasable Potentially Prebiotic Nucleotide Activating Agent.Mariani A, Russell DA, Javelle T, Sutherland JDJ Am Chem Soc 140(28): 8657-8661 (2019)
Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism.Patel BH, Percivalle C, Ritson DJ, Duffy CD, Sutherland JDNat Chem 7(4): 301-7 (2015)
Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions.Powner MW, Gerland B, Sutherland JDNature 459(7244): 239-42 (2009)