Few people will have heard of G-protein-coupled receptors (GPCRs) until fairly recently, when Brian Kobilka and Robert Lefkowitz won the Nobel Prize in Chemistry for their work on them in 2012. The prize recognised their achievement in illuminating the fundamental functions of GPCRs – an unwieldy moniker that is nearly impossible to remember for anyone who doesn’t work with these receptors constantly.

Then in mid-April 2016, ETH Pioneer Fellow and former ETH doctoral student Martin Ostermaier joined with Aurélien Rizk and Luca Zenone to found a company based on this Nobel prizewinning work. The three up-and-coming researchers called their company InterAx Biotech; they have now officially established it and registered it as a spin-off of both the ETH Zurich and Paul Scherrer Institute.

Major implications for pharmaceutical research

People outside the field might wonder at how quickly this basic research has moved into practice, but Ostermaier says it’s no surprise: “Even before I began working on my doctorate at ETH Zurich, I knew how important GPCRs would be for drug research.” One third of today’s medications target these receptors, which are found in the outer layers (membranes) of cells in the human body. These drugs range from beta-blockers for treating high blood pressure to antipsychotics for mental illnesses. Science has identified about 800 different GPCRs, although just 370 of them are suitable as a docking site for medications; thus far only one sixth of these can be used for pharmacological purposes.

Often what happens is that pharmaceutical researchers will have identified a GPCR they wish to target, but lack the methods for accurately testing whether their drug works as planned, explains Ostermaier. It would be a huge step forward for all GPCR-medication research if a method were found that made it possible to find medications for other usable GPCRs, or improve medications for the GPCRs already targeted. “This is precisely the issue we are working to resolve,” Ostermaier says.

Customised biosensors

InterAx is developing new kinds of biosensors that increase the speed and accuracy of testing if and how a particular drug affects a certain receptor. The biosensors work based on the fact that a receptor’s state changes as soon as a drug docks with it. Each state triggers a signal path that has a specific effect in the cell. However, because a GPCR can adopt various states, it can send different signals.