Genomics and Molecular Medicine

Genomics and Molecular Medicine is the major research focus of IGIB. From large collaborative projects like the Indian Genome Variation Consortium to exploring genetics of complex disorders several groups at IGIB are involved in studying the molecular basis of human diseases.

* Indian genome variation: discovery, functional relevance and application

IGIB scientists have been the core of a consortium of Indian scientists who mapped genetic variation amongst the ethnically and linguistically diverse populations of India. Insights gained from this data has now prompted many projects which aim to test the functional importance of these variations in establishing phenotypic diversity, for instance, in susceptibility to diseases and efficacy of drugs. Pharmacogenomics of drugs for asthma and epilepsy is a prime example where efforts are on to correlate genetic variation to drug efficacy. The spectrum of polymorphisms in genes linked to complex disorders like diabetes, cardiovascular and neuropsychiatric disorders in the Indian population are also being explored.

* Genome wide analysis of motifs and their functional role in gene expression.

Several groups at IGIB are involved in cartography of functional elements, including methylation sites, transcription factor binding sites and non-coding RNA using next-gen sequencing. Quadruplexes, structural motifs formed by G rich sequences, have been well characterized in vitro but their existence and importance in vivo has proven elusive. Genome analysis across genomes led to the identification of a large number of potential quadruplexes in prokaryotes and eukaryotes. Their prevalence in functionally important sites in the genome suggests a potential role in gene regulation. Genome-wide effects of quadruplex binding proteins and ligands provide a handle for mechanistic studies into the function of quadruplex motifs.

* Prediction of microRNA-target interaction and study of their biological significance

Naturally occurring small RNAs that regulate the expression of target genes have grown in numbers, diversity, scope of biological phenomena they regulate and consequently therapeutic potential. Mutually corroborating predictions from software programs refined by structural analyses were used to identify miRNAs that target HIV1 genes, mediators of apoptosis and inflammation, insulin signalling genes and alternative untranslated regions of target genes. The understanding of miRNA-target interaction gained through experimental validation of these targets has led to new interests: design of artificial miRNAs, regulation of alternatively polyadenylated transcripts and programmable networks using miRNA-target interaction.