The new biosensor represents a significant milestone in overcoming the technical challenges of monitoring receptor activation inside living cells
Researchers at the Indian Institute of Technology Kanpur (IIT Kanpur) have developed a novel antibody-based biosensor that can monitor the activation of G protein-coupled receptors (GPCRs) in live cells. GPCRs are the largest family of receptor proteins in human cells and are targeted by more than one-third of all clinically prescribed medicines.
Led by Prof Arun K Shukla, the research team has been investigating GPCR biology for over a decade. GPCRs, because of their central role, are considered some of the most important gateways for developing new drugs and therapies. The new biosensor represents a significant milestone in overcoming the technical challenges of monitoring receptor activation inside living cells.
The IIT Kanpur team developed an engineered antibody (nanobody) sensor that binds to GPCRs only upon activation and in association with arrestins. When the receptors are activated by their ligands, the nanobody comes into close proximity, triggering an enzymatic reaction that produces a measurable luminescence signal.
“The beauty of this biosensor is that it does not require any modification of GPCRs, and still, it can report their activation by ligands. This opens up possibilities for imaging these receptors in disease contexts,” said Prof Arun K Shukla, Professor, IIT Kanpur who led the study.
“The versatility of this sensor allows us to monitor the localization of GPCRs in different sub-cellular compartments, which in turn tells us about their downstream signalling mechanisms. This is an important development in understanding GPCR signaling for novel drug discovery”, says Annu Dalal, a Ph.D. student at IIT Kanpur and one of the lead authors in this study.
The project was carried out in collaboration with Prof Josef Lazar’s laboratory at the Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague. It was supported by an Indo-Czech joint research initiative funded by the Department of Science and Technology (DST), Government of India. The findings are published in the peer-reviewed journal Proceedings of the National Academy of Sciences (PNAS), USA.
Other members of the IIT Kanpur research team include Parishmita Sarma, Manis Yadav, Sudha Mishra, Nashrah Zaidi, Divyanshu Tiwari, and Nabarun Roy.
This breakthrough strengthens IIT Kanpur’s long-standing research in molecular and structural biology and opens up new possibilities for advanced drug discovery and therapeutic innovation.
