A technique recently developed by Yimon Aye’s group at Oxford Chemistry, and published today in the journal Cell, takes a key step towards decoding signalling processes in individual types of cells.
Reactive small molecules known as electrophiles are indicators of stress or danger in living organisms. Sentinel proteins detect them quickly, allowing information about threats to be rapidly passed on to other proteins, ultimately leading to important decisions at the level of the cell or the organism. Identifying such sentinel proteins and their location in organisms is instructive for both biological understanding and drug discovery. However, these signals often elude current methods.
Now, Prof Yimon Aye’s group in the Department of Chemistry has developed a method that will help decode this signalling process. The team’s method can be used on live nematode worms to map organ-specific responses to a particular electrophile molecule. The new technology, named OS-Localis-REX, provides a new way to decipher the wide variety of chemical signalling events happening in specific locations in a live animal.
Electrophile-signalling processes are wired into the emergency systems of the cell. Electrophile-responsive proteins can thus help us to understand intrinsic emergency response pathways, and how to develop new drugs. These signalling events are conserved across evolution, and directly govern how organisms defend themselves against chemical stress and manage their own physiological functions.
The work has been funded by the European Research Council and Novartis, and was conducted in collaboration with partners in Switzerland and the USA.
For more information, see the article in Cell.
Thumbnail image: Liu et al / Cell (Elsevier).