Site selective aminoacylation of nucleic acids toward expansion of the genetic code
Project ID: 2531bd1641
(You will need this ID for your application)
Research Theme: Physical Sciences
Research Area(s):
Chemical reaction dynamics and mechanisms
Synthetic organic chemistry and supramolecular chemistry
Chemical biology and biological chemistry
UCL Lead department: Chemistry
Lead Supervisor: Matthew Powner
Project Summary:
Protein synthesis is orchestrated by transfer RNAs (tRNAs) that are covalently attached to their cognate amino acids. This attachment sets the genetic code allowing sequence specific protein synthesis. Nature employs a limited set of (20-22) amino acid building blocks for protein synthesis, which limits the functional and structural diversity of proteinogenic peptides.
Expanding the genetic code to incorporate new building blocks, with new chemical and physical properties can be transformative, enabling diverse applications not available within the native pool of biology’s canonical peptides. This has led to remarkable advances across protein science from imaging and control of function to the discovery of novel therapeutics.
In this project we will develop chemical and biochemical protocols to uncouple RNA aminoacylation from enzymatic constraints to develop a new transformative technology for expansion of the genetic code. Our novel approach will be based upon mechanistic selective chemical modifications of RNA, and we will further investigate the chemical reactivity that underpins this selectivity, to shed further light on the origins of the central dogma of molecular biology and the genetic code.
The project will build upon our groups extensive expertise in elucidating the chemical mechanisms that underpin life’s development, and our recent discovery that aminoacyl thiols selectively aminoacylate RNAs in water at neutral pH (Nature 2025, 644, 933–944). We will develop this reactivity to expand the chemical repertoire of building blocks that can be selectively charged to an RNA 2’3’-diol.
The successful candidate will join a group of highly motivated scientists working to elucidate the chemistry that underpins the origins and evolution of life on Earth. The Powner group uses chemical synthesis and systems chemistry to explore the chemical reactions that underpin biology, whilst developing novel, robust, green (bio)chemical reactions that can improve the synthetic and catalytic strategies available to access key biochemical targets.