March 11, 2021—The aryl hydrocarbon receptor (AhR) is a cellular sensor that interacts with a wide variety of molecules. When it binds to those molecules, it shuttles to the nucleus of the cell, where it drives gene expression essential to a variety of processes, including metabolism and immune responses. Because its deregulation is associated with cancer and autoimmune diseases, AhR is an attractive target for therapeutic drugs. To design such drugs, it is important to understand the binding properties of AhR’s molecular interactions to allow specific pharmacological targeting of one interaction without affecting others.
Working with colleagues from Germany, Ludwig Oxford’s Pedro Moura Alves has developed a new method for identifying and characterising those interactions. Published in the journal Biosensors, their approach uses a technique called microscale thermophoresis, which overcomes many of the disadvantages with existing technologies to allow a faster and more robust investigation of these binding events. Key to their innovation is the development of a new system for generating larger amounts of stable, purified human AhR protein by fusing the AhR to a protein tag and co-expressing the AhR in complex with its interacting nuclear partner ARNT.
This new method will not only allow the further investigation and discovery of AhR interactors for biomedical research but also has the potential to underpin future screens for drugs that can be used to treat AhR-associated diseases.