Using yeast to uncover a common drug's secrets

Yeast © Alain Herzog

Yeast © Alain Herzog

An anti-inflammation drug’s well-kept secrets have finally been uncovered thanks to a type of yeast; a discovery that will impact treatments for other diseases and limit side effects.

Sulfasalazine is a frequently used drug, but its anti-inflammation mechanism has remained, to date, poorly understood. However, a team from EPFL’s Laboratory of Protein Engineering has now been able to elucidate this mystery. They have identified the specific protein that is inhibited by the treatment. The results, published online in Nature Chemical Biology on the 17th April, open the way to new applications and complementary treatments that will reduce side-effects.

The goal of this research was to identify those proteins that are targeted by drugs. In order to achieve this, the scientists used yeast. When specially engineered, they produce human proteins and enable the identification of molecular interactions between these proteins and a given drug.

The team from the Laboratory of Protein Engineering had as its starting-point the need to identify the drug’s targets. Thanks to the use of engineered yeast, they were not only able to determine the mechanism of action of sulfasalazine, but also to discover new protein targets for other important drugs. Christopher Chidley, Hirohito Haruki, Miriam Grønlund Pedersen, Evelyne Muller and Kai Johnsson worked for nearly four years to develop this method, which forms part of Christopher Chidley’s thesis.

Discoveries in prospect

Sulfasalazine is used to treat intestinal inflammation and also rheumatoid polyarthritis. By understanding how the drug works, Kai Johnsson’s team believe that other diseases could be treated. They also hope to reduce side-effects by testing the administration of complementary molecules. “We have clear theories that we want to experiment in the near future”, adds Kai Johnsson.

The research being performed in this domain takes place within a larger context. The Laboratory of Protein Engineering is part of the National Center of Competence in Research (NCCR) Chemical Biology. This program is financed by the Swiss National Science Foundation (FNS), and is also associated with the University of Geneva.


Source article:
A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis. Christopher Chidley, Hirohito Haruki, Miriam Grønlund Pedersen, Evelyne Muller & Kai Johnsson, Nature Chemical Biology, 2011.

Author: Nicolas Guérin

Source: EPFL