Image Courtesy: IIT Kanpur
Prof Arun Kumar Shukla, a structural biologist and a professor in the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology, Kanpur, has won the prestigious Infosys Prize 2023 in Life Sciences, for his contributions to the understanding of G-protein coupled receptors (GPCRs), a crucial aspect of cellular activity.
This prize is a recognition of Prof Shukla’s research which produced beautiful illustrations of the mechanics behind the selective activation of signalling pathways downstream of GPCRs. These and other findings offer a basic comprehension of the context-dependent roles of GPCRs and propose a fresh approach to the development of innovative treatments.
GPCRS AND THEIR SIGNIFICANCE
All live cells move ‘information’ throughout the cell, from the inside to the outside, and vice versa, in order to maintain the basic operations of the cell. The ongoing ‘trafficking’ of information is done by protein molecules known as ‘receptors’. The largest and most significant of these receptors are GPCRs that are found on the cell’s surface and react to different stimuli from the outside world. They perform vital cellular tasks essential for regulating numerous bodily processes, including development, hormone responses, and feelings. Furthermore, medications for a variety of illnesses, including mental disorders, cancer, hypertension, and cardiac diseases, target GPCRs. It is estimated by researchers that between one-third and half of all medications that are sold, function by binding to GPCRs. Thus, a deeper comprehension of GPCR function can aid in the development of medications with few side effects and maximum effectiveness.
However, life-saving drugs, including those for hypertension, may not only cause severe side effects, but can also cause resistance for medications for various other diseases.
Understanding GPCRs in terms of their structure, function, and regulation is the focus of Prof Shukla’s study. Our tissues and organs are mostly made up of cells, which interact with one another to alter their size, shape, and function. Brain illnesses, malignancies, heart ailments, and developmental anomalies can all be caused by the dysregulation of cell-cell signalling.
GPCRs are a key component of signalling and play a complex role in nearly all bodily physiological processes. According to Prof Shukla’s research, agonists—specific activators that selectively engage one of the two key pathways downstream of GPCRs—can reduce the adverse effects of frequently prescribed medications. The idea of biased agonists with the ability to control GPCR signalling can be used to create medications for various human illnesses.
Prof Shukla has successfully developed a platform for synthetic antibody technology and used it to construct modulators to regulate GPCR trafficking and signalling, and sensors to investigate GPCR activation. These instruments have broad ramifications on hitherto undiscovered facets of GPCR biology. Understanding the structural biology of membrane proteins, such as GPCRs and their signalling complexes, is a key component of his study program.
Using a framework for synthetic antibody technology, Prof Shukla’s lab has created sensors that examine the operations of GPCRs and in the creation of national cryo-electron microscopy facilities—a technique that is essential to the advancement of basic science in India. He has built small ‘nanomachines’ through which he has discovered that even a single alteration in GPCR can affect its interaction with other proteins and become activated. His research data can be used to build more effective medications with precise cell targeting.
An MSc from Jawaharlal Nehru University, New Delhi, Prof Shukla completed his PhD at the Max Planck Institute of Biophysics in Frankfurt, Germany. Prior to joining IIT Kanpur in 2014, he worked as a research associate and assistant professor at Duke University, North Carolina.
He is a recipient of DBT Wellcome Trust India Alliance Senior Fellowship, National Bioscience Award (2018) and the Shanti Swarup Bhatnagar Prize (2021).
*The writer is a postdoctoral fellow in the department of Mathematics, IIT Kanpur, doing research in the field of Numerical Analysis. He holds a joint MSc-PhD in Mathematics from IIT Kharagpur.
