Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Cellular Thermal Shift Assay (CETSA): From drug targets to horizontal cell biology (#790)

Nayana Prabhu 1 , Lingyun Dai 1 , Tianyun Zhao 1 , Ying Yu Liang 1 , Wendi Sun 1 , Pär Nordlund 1
  1. Nanyang Technological University, Sinagpore, SINGAPORE, Singapore

The Cellular Thermal Shift Assay i.e. CETSA is based on the biophysical principle of ligand-induced thermal stabilization of proteins. At inception about 5 years ago, CETSA was considered a tool for drug-target deconvolution and mainly used to study direct target engagement in situ. Using quantitative mass spectrometry, proteome-wide CETSA (MS-CETSA) was established, which allows off-target binding as well as downstream effects to be discovered, in addition to direct drug-target interactions. MS-CETSA has since then been used widely in the pharmaceutical industry for such studies and is currently a valuable tool for biomedical research and drug development.

Today, MS-CETSA has evolved to encompass several other applications including novel ways to study cell biology. With the advent of a highly sensitive multidimensional implementation of MS-CETSA, comprehensive studies of protein level changes as well as stability changes are plausible. In addition, MS-CETSA can also be used to access binding of physiological ligands to proteins, such as metabolites, nucleic acids and other proteins. Such studies will aid in understanding “Horizontal Cell Biology” where modulations of protein interaction states (PRINTs) are studied (as opposed to the “vertical information” focusing on the protein and RNA levels) to provide new insights on cellular functions and processes.