Dr Ewen D D Calder

Chancellor's Fellow (Health and Life)

Biography

Background

Ewen Calder received his PhD in Chemistry from the University of Glasgow in 2015, working in the lab of Prof. Andrew Sutherland on new methodologies for the synthesis of nitrogen containing heterocyclic molecules. He carried out postdoctoral work at the University of Oxford, splitting his time between the labs of Prof. Stuart Conway and Prof. Ester Hammond. There his work focused on the design, synthesis and testing of photo- and hypoxia-activated pro-drugs of clinical KDAC inhibitors. In 2019 he moved to the lab of Dr Louise Walport at the Francis Crick Institute and Imperial College London, for further postdoctoral work where his focus was on developing and optimising an advanced form of mRNA display. In 2024 he moved to the University of Edinburgh to take up his current position as a Chancellor's Fellow (Health and Life) between the School of Chemistry and the Institute for Regeneration and Repair.

Research summary

mRNA display, peptide chemistry, unnatural amino acids, chemical tools, chemical biology, SUMO, Ubiquitin-like proteins

Current research interests

I am a Chancellor's Fellow (Health and Life) based between the School of Chemistry and the newly founded Institute for Regeneration and Repair. My current research area is the use of the Random non-standard Peptide Integrated Discovery (RaPID) system of mRNA display to discover novel peptide-based chemical tools. RaPID mRNA display allows the screening of vast (>10 trillion members) libraries of macrocyclic peptides against protein targets, and frequently generates hit compounds with very tight binding and high selectivity. These libraries are orders of magnitude larger than classical high-throughput screening or other display technologies. The RaPID system also allows the incorporation of unnatural amino acids into these peptides, enhancing their potency, permeability and stability. My main area of focus is on the discovery of chemical tools to modulate the enzymes involved in SUMOylation. SUMOylation is an important, highly dynamic post-translational modification which involves the conjugation of a small ubiquitin-like modifier (SUMO) to a lysine residue of a protein. SUMOylation is important in the regulation of a multitude of cellular processes, including cell cycle progression, genome stability, transcription, and DNA repair. Misregulation of SUMOylation is implicated in a wide range of pathologies including Huntington’s disease, amyotrophic lateral sclerosis, Alzheimer’s disease, and many cancers. Additionally, due to its roles in innate immunity, the enzymes mediating SUMOylation are targeted by many pathogens.

Past research interests

I have previously worked in a variety of areas including mRNA display method development (Walport lab), development of hypoxia- and photo-activated prodrugs of KDAC inhibitors (Conway lab) and natural product synthesis and development of new synthetic organic chemistry methodologies (Sutherland lab).
This article was published on