Meet Nimit Desai

Nimit DesaiHello! I’m Nimit Desai, and I’m a senior at the North Carolina School of Science and Mathematics. I have been involved in research in biochemistry and receptor biology for the past two years, and have absolutely loved it – this area of research mirrors my passion for biology, chemistry, and other disciplines of science. Other than my research experience, I am also able to explore my passion in science by being an Editor-in-Chief for my school’s scientific research journal, Broad Street Scientific. In and after college, I aspire to integrate my passion for medicine and the sciences with my deep interest in entrepreneurship to develop solutions to healthcare problems. On top of my passions for science, medicine, and entrepreneurship, I absolutely love basketball. I am a die-hard Miami Heat Fan (yes, even after LeBron left), and in my free time, I love to walk to my school’s gym and play pick-up basketball games. I also love to explore new places and other parts of the world!

Given my interest in the sciences and exploring the world, it’s no surprise to me that I’m so excited for the trip to Beijing! I’m looking forward to not only sharing my research with others, but also to hearing about the cool research other high school and college students conduct in China and other countries. I’m equally excited, however, to explore different places, foods, and cultures in China!

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The Project:

Heterotrimeric G protein-coupled receptors (GPCRs), a family of cell surface receptors, are targeted by ~50% of prescription drugs on the market today. A ligand binding to a GPCR can lead to downstream signaling through the G protein pathway, β-arrestin pathway, or both. However, studies have shown that ligands may exhibit biased properties, resulting in differential activation of downstream signaling pathways. The purpose of this study was to identify biased ligands for CXCR3A, a chemokine GPCR, and to understand the underlying mechanisms controlling this bias. Bioluminescence Resonance Energy Transfer (BRET) and GloSensor cAMP assays were conducted on ligand-treated cells expressing the CXCR3A receptor to monitor G protein and β-arrestin activity, and results were confirmed with western blots. Site-directed mutagenesis was used to then identify structural components important to bias mechanisms. The results demonstrate that VUF11418 is a G protein biased ligand, and VUF10661 is a β-arrestin biased ligand. The data are consistent with GRK phosphorylation creating a “barcode” on the tail end of the receptor, leading to differential downstream signaling. By providing the capability to selectively activate certain beneficial pathways and not activate harmful pathways, the identified biased ligands can potentially be used to improve therapeutics for inflammatory disorders and dysregulated T-cell activation, both of which are fundamental to our immune system.

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