How has your work on the biology of G-protein coupled receptors (GPCRs) helped pharma companies increase the efficacy of medicines for common diseases like diabetes, hypertension etc.?
About half of the currently prescribed medicines work through GPCRs by turning them on or off. However, the signaling mechanism downstream of GPCRs is very complexes and involves multiple pathways operating in parallel. These multiple signaling pathways operating in parallel often drive the desired outcomes and side effects of medicines. Our work has provided fundamental insights into how we can segregate or selectively activate these different signaling pathways to minimise the side effects while maintaining the desired outcomes of prescribed drugs. We have also discovered that nature has already designed some GPCR like receptors that harbor the ability to preferentially activate selected signaling pathways. These receptors should provide important clues to segregate the complexity of GPCR signaling with direct therapeutic implications.
What is the next research question you are tackling on GPCRs or related research areas, and what would be its impact on patients?
We are now trying to understand the molecular mechanism of GPCR signaling using multiple complementary methods such as cryo-EM, cellular assays, and animal models. The long-term vision of our research is to understand the intricate details of GPCR activation, downstream signaling, and discover new signaling pathways relevant to therapeutic design. We also utilise synthetic antibody platform to generate and characterise novel sensors and modulators of GPCR signaling with potential therapeutic applications as well. We have also identified some interesting leads in terms of new receptors that are very distinct from prototypical GPCRs in terms of their functional paradigms, and we are trying to study them in more detail. We have also started exploring pathogen-GPCR interactions such as those of bacteria and viruses from an angle of antimicrobial resistance and novel therapeutic avenues in future pandemics.
Squeezed by thinning margins and increasing compliance costs, pharma companies are finding it very difficult to fund R&D into new medicines. How can collaborations with labs like yours at IIT Kanpur bridge this gap?
Collaboration with academic laboratories may provide important leads to pharma companies, which they can build on quickly in terms of translational outcomes. While most academic laboratories are engaged in discovery biology, the major pharma companies are interested in downstream application-oriented development programs. Thus, it makes a lot of sense for the two enterprises to work together in order to combine discovery biology and translational research. It would be very effective and productive academia-industry collaborations can be established from the very beginning based on specific targets, biology, and disease focus.
What does the Infosys Prize 2023 for Life Sciences mean to you on a personal level? And for your team and institution?
It is a great honour that our work has been recognised by the Infosys Prize, and all the credit goes to the wonderful students and fellows in our laboratory. In my decade long journey in Indian science, my interaction with wonderful students and fellows has clearly been the highlight of my experience. I am so very happy for our students. I also feel that it is recognition of our research domain focused on structural biology of membrane proteins, which was considered a taboo in India at one point because it is very challenging. It feels great that our work has inspired several outstanding scientists to work in this incredibly challenging but highly rewarding research area in India. It has also been an incredible experience to set-up our research program at IIT Kanpur, arguably one of the best places in the country to do cutting-edge science while having an opportunity to teach and interact with incredibly bright young minds. If I had to do it all over again, I would still do it at IIT Kanpur hands down.