Research Projects

In India, there is a lack of research on viral infectious diseases at the population level, particularly in understanding the genetic underpinnings of varying disease severity in patients. Genetic polymorphisms can play a significant role in the susceptibility and pathogenesis of viral infections, as seen in the famous hepatitis C virus (HCV) genome-wide association studies (GWAS). However, the Indian population has not been systematically catalogued for variation in immunity genes, making it difficult to use large-scale studies like GWAS. This presents an opportunity to measure the variation in important immunity genes, such as IFN genes, first in the healthy population. The proposed proposal aims to understand the molecular function of a single nucleotide polymorphism (SNP) in the important type III IFN, IFN-L1 gene promoter. A well-powered study from Thailand reported the association of rs7247086, an SNP in the distal promoter region of IFN-L1, with severe dengue disease. The study hypothesizes that the SNP functions by altering the transcriptional activity of the IFN-L1 promoter. To test this hypothesis, the researchers will perform promoter and enhancer activity assays using transient and stably transfected cell lines and EMSAs. They will also generate cell lines with the two alternate alleles using gene editing technology and use a health cohort established by the PI under a Wellcome Trust DBT project to identify individuals carrying different alleles at the SNP site. The results will comprehensively characterize the functions of the SNP in dengue infections and establish its role in regulating transcription of the IFN-L1 gene.