Kanpur, October 1, 2021: The Indian Institute of Technology, Kanpur (IIT-K) and The University of Queensland (UQ) today published the results of a path-breaking international collaborative research in inflammatory disease. The findings, published in ‘Molecular Cell’, a peer-reviewed scientific journal on molecular and cell biology, throws new light on a protein receptor, C5aR2, that plays an important role in the moderation of many immune and inflammatory processes and explores its use as a potential therapeutic target for treating multiple chronic inflammatory diseases. The research saw international collaboration between Professor Arun Shukla, IIT Kanpur, India with researchers Asuka Inoue, Tohoku University, Japan and Stéphane A. Laporte, McGill University, Canada.

This is the first time that researchers have identified key molecules within the immune system that may help fight the inflammation that drives chronic inflammatory diseases. The findings of the research will help further research in novel drug molecules that can act on the receptors for C5a, a potent immune molecule that is linked to multiple immune-linked inflammatory diseases such as cancer, rheumatoid arthritis, sepsis and even COVID-19.

Prof. Abhay Karandikar, Director, IIT-K said “The publication of the research paper on inflammatory diseases is testament to the capabilities of IIT Kanpur to undertake challenging research at the frontiers of science. We are optimistic that the findings will lead to new light in the fight against chronic inflammatory diseases.”

UQ Prof. Trent Woodruff said the research investigated the part of the immune system responsible for the body’s natural response to pathogens and injury, known as the ‘complement system’. He said, “When activated inappropriately, the system drives inflammatory diseases such as sepsis, COVID-19, stroke, heart attacks, cancers and brain illnesses. It’s been really challenging for researchers to understand how this protein is activated due to its unusual structure.”

“Instead of coupling with cell-signalling proteins, C5aR2 relies on signal regulating proteins known as β-arrestin proteins. Our study investigated interactions between the C5aR2 and β-arrestin proteins, while screening for molecules that activated a connection between the two. We found key and specific cell signals present when the C5aR2 was activated, which may act to boost the immune system’s response in inflammation,” added Prof. Woodruff.

Co-investigator Professor Arun Shukla said the findings provided a framework for further exploration of β-arrestin proteins for their therapeutic modulation in disease. “We are now working to progress these research findings into disease models and potentially enable scientists to design novel drug molecules targeting C5aR2 to treat inflammatory disorders”.

Link to the paper: https://www.cell.com/molecular-cell/fulltext/S1097-2765(21)00741-3

About Prof. Arun. K. Shukla

Dr. Arun Shukla obtained M.Sc. in Biotechnology from the Jawaharlal Nehru University (JNU) in New Delhi and pursued his Ph.D. with Prof. Hartmut Michel at the Max Planck Institute of Biophysics in Frankfurt, Germany. Dr. Shukla subsequently joined the laboratory of Prof. Robert J. Lefkowitz at Duke University as a Research Associate and worked in a very close collaboration with Prof. Brian Kobilka's laboratory at Stanford University. Prior to joining the IITKanpur BSBE faculty in April 2014, he was an Assistant Professor in the Department of Medicine at Duke University, North Carolina, USA. He has recently been awarded the Shanti Swarup Bhatnagar Award, 2021.

About Prof. Trent Woodruff

Dr. Woodruff is a Professor of Pharmacology at the University of Queensland who leads a research team aiming to find new therapeutic treatments for neurodegenerative disorders. Prof Woodruff's specific research revolves around the innate immune system in the brain, and the role of neuro inflammation in propagating disease. A key focus of his current work is testing new drugs developed at the University of Queensland in models of motor neuron disease (amyotrophic lateral sclerosis), Huntington's disease, and Parkinson's disease, as well as maintaining an active interest in acute inflammatory disorders including sepsis and ischemia-reperfusion injuries.