Research
Within the broad field of computational biology, we focus on eukaryotic gene regulation and its evolution. We develop computational approaches to harness the huge amount of biological data (genomes, transcriptomes, proteomes, microarray, Chip-seq etc) to answer specific biological questions pertaining these domains. Please refer to our publications to get a better sense of what we do. Collaboration ideas are welcome. Here is representative list of questions we are currently pursuing.
Characterizing transcription factor DNA interactions
Transcription factors (TF) bind to short and often degenerate DNA motifs. From an information-theoretic viewpoint there is insufficient information in these motifs to accurately identify the binding sites. A fundamental question is - what provides the requisite specificity of TF-DNA interactions. We are pursuing a number of independent approaches to address this, including investigation of inter-position dependence within binding sites, integrating evolutionary and epigenomic information, and identification of functional subclasses of binding sites for a TF. Several studies have suggested that many TFs recognize distinct motifs with functional implications. We are collaboratively studying the functional modalities of CTCF protein and its implications on embryonic development.
Identifying regulatory polymorphisms
While numerous association studies (GWAS) have revealed polymorphisms associated with several human diseases, clinical progress is hampered by our lack of understanding of functional consequences of polymorphisms (SNP), especially, the non-coding SNPs.We are developing integrative strategies to identify SNPs likely to underly the diseases, with a focus on hypertension and cardiovascular diseases. A long-term goal in this context is to be able to predict the disease risks for specific haplotypes and personalize treatments for genetic diseases.
Evolution of transcriptional regulation
Gene duplications provide a crucial fodder for evolutionary innovation and what determines the fate of a duplicated gene is of interest to us. Expression and coding sequence represent two pathways of divergence; relationships between these pathways of divergences, especially the ones with quantifiable functional consequence, may elucidate the selection pressures during the evolution of a gene family. For instance, We have found that for TF gene paralogs the expression divergence is inversely related to the divergence in their DNA binding motifs. Similar investigations of other aspects of functional divergence, neo-functionalization and sub-functionalization etc. are in progress. In the long term we are also interested in investigation of the evolution of developmentally important regulatory networks based on the duplication and diversification of individual genes in the network.
Natural selection on regulatory elements
Polymorphisms in the non-coding portion of the human genome are likely to underlie significant components of the inter- and intra-species phenotypic variability. If so, these genomic regions are likely to be evolving under natural selection. However, the non-coding region is a heterogeneous mix of functional elements, each under potentially varying selection regimes. Our previous results indicate that in general, human-specific and primate-specific binding sites may be evolving under positive selection. We have extended similar techniques to study signatures of selection in a variety of functional elements, both coding and non-coding.Micro-RNA involvement in viral-host interaction
Micro-RNAs (miRNA) are repressive regulatory genes that can target other RNA molecules via sequence-specific binding and mediate their cleavage and degradation. Several endogenous biological processes are mediated by evolutionarily conserved miRNAs across many organisms. Plants and invertebrates employ their miRNA in defense against viruses by targeting and degrading RNA encoded by the virus. Viruses also encode miRNAs and there is some evidence to suggest that virus-encoded miRNAs may target specific host genes. We are investigating the scope of miRNA involvement in host-pathogen warfare.
