Transcription Regulation

INFECTIOUS DISEASES / Parasitic Diseases

Research Interests

Structure, dynamics and folding of protein-nucleic acids and protein-protein complexes: Metabolomics

Description of Research

Molecular mechanism of protein-nucleic acid interactions
The main theme of the group is to understand molecular mechanism of interactions between protein and nucleic acids that exhibit a wide spectrum of sequence and shape specificity. The understanding of molecular mechanism of the interaction by highly conserved and abundant RRM proteins will help in formulation of a general code of nucleic acid interaction. This is likely to help in understanding how different set of information is decoded from a limited repertoire of genetic code. Nascent mRNAs, the information carriers, in eukaryotes often called the primary transcripts, undergo extensive chemical modification to produce mature mRNAs before they are directed for protein synthesis.

These modifications are performed by a class of proteins called RNA binding proteins. Although the canonical structure of the well-studied RNA-binding domains is generally quite well conserved and restricted, this domain can readily have subtle structural adaptations and is able to recognize a wide spectrum of different RNA and DNA sequences and shapes. The group effectively uses solution-state NMR spectroscopy, X-ray crystallography and other biophysical tools to decipher the molecular mechanism of different protein nucleic acid interactions.
Many RNA recognition motifs (RRMs) are known to unfold and assemble incorrectly, leading to protein aggregates that cause diseases. In this context we study unfolding and aggregation behaviour of RRMs using solution- and solid-state NMR spectroscopy, fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence spectroscopy.

Metabolomics for Bio-marker discovery
We use solution-state NMR for metabolomics analyses. Among the techniques used for studying metabolites high-resolution solution-state NMR spectroscopy has the advantages of being non-destructive, quantitative, robust and highly reproducible. It is a non-equilibrium perturbing technique that provides detailed information on solution-state molecular structures, based on atom-centred nuclear interactions and properties, which can also be used to explore metabolite molecular dynamics and mobility. It allows the simultaneous detection of a wide range of structurally diverse metabolites, providing a metabolic ‘snapshot’ at a particular time point. Metabolite concentrations down to the micromolar range are readily detectable in biofluids (urine, serum, plasma, saliva) and cell or tissue extracts. We have recently identified metabolic dysregulation in Dengue, Chikungunya, HIV and HEV patients and deciphered the metabolic pathways in fungus and plants. 

Recent Publications