DST-INSPIRE project theme

Inflammatory bowel disease (IBD) is an umbrella term that refers to persistent ulcerations of the digestive tract, mediated by chronic inflammation. IBD patients are commonly put into lifelong medications to ease the disease symptoms, however, response of different patients to various anti-inflammatory drugs is found to be fairly heterogeneous in pattern. NF-κB factors are the well-known master regulators of major inflammatory cascades in the body, and NF-κB activation is markedly upregulated in various inflammatory diseases including IBD. A number of research groups across the globe are interested in probing NF-κB to investigate treatment options for IBD, but the path from scientific speculation to experimental confirmation is still elusive. 

Under the scheme of Inspire faculty fellowship, I want to develop a project on establishment of an ‘Inflammation-on-a-Chip’ platform to enable cell culture and perform drug screenings in miniaturized volumes. An appropriate NF-κB fluorescence reporter cell line of colorectal origin shall be established as the in vitro cellular model of IBD. A miniaturized droplet-based microarray platform shall be used to culture these cells and perform screening with large panels of FDA approved anti-inflammatory drugs. Effects of drugs on inflammation, as evident by NF-κB expression in the cells, shall be evaluated by fluorescence readouts. Next, mRNA will be isolated from each cell sample on the hydrophilic spots of the ‘Inflammation-on-a-Chip’ platform and converted to cDNA with barcoded primers, followed by next generation sequencing. Sensitivity and resistance of NF-κB reporter cells to drugs will be associated with the global transcriptomic signatures post drug screening. The key findings of the study shall be validated with IBD biopsy samples procured from AIIMS, New Delhi.