Research Activities

                                                                   

Research Funding

 

Completed Minor Research Project (Institutional)

​

Title: Information Driven Study of SNPs from Lipopolysaccharide Binding Protein (LBP) and Toll like Receptor-4 (TLR4) using bioinformatics tools.

​

Duration: 1 year (09/12/2020-09/12/2021), Amount: 15000 INR, Ref: No: 826/B/2020 dated 09/12/2020

 

Current Research

My current research activities are:

Computational exploration of non tuberculous mycobacteria: I am exploring Mycobacterium ulcerans, Mycobacterium kansasii, Mycobacterium abscessus complex and Mycobacterium avium complex using genomic, phylogenetic, network analysis and comparative genomics approaches to understand the genomic architecture, diversity, pathogenomic evolution, virulence and resistance patterns. Furthermore, I am applying immunoinformatics techniques to design suitable epitopes and screening potential drug compounds that can combat the pathogen.

​

Insilico analysis of clinically relevant SNPs from human Lipopolysaccharide (LPS) binding protein, Toll like receptor 4 and cyclic GMP-AMP synthase: In this context, I investigated SNPs of Lipopolysaccharide (LPS) binding protein (rs2232618) linked to sepsis, pattern recognition receptors like Toll like receptor 4 (rs4986790, rs4986791), 8 (rs3764880) and cyclic GMP-AMP synthase (cGAS) associated with tuberculosis and extra pulmonary tuberculosis. These SNPs are known to initiate immune response of the host. I have applied various computational techniques to comprehend the implication of the SNPs on structural and conformational changes that interferes with normal functionality, ligand binding and altered susceptibility to sepsis, tuberculosis and extra pulmonary tuberculosis. The findings from these studies have been validated by my experimental and clinician colleagues/collaborators.

​

Exploration of of enriched pathways and genes in Type 1 diabetes: Type 1 diabetes (T1D) is a multifactorial, polygenic complex autoimmune disease responsible for damaging pancreatic islet β cells. I used bioinformatic tools to analyse enriched biological pathways, functions, enrichment clustering, networks and interactomes from documented T1D-associated genes. Enrichment analysis of T1D-associated genes highlighted the impact of immune-linked machineries in metabolism, disease progression and aetiology of type 1 diabetes. Additionally, the work identified a number of significant pathways associated with various genes that are crucial for designing precision medicine–based therapeutics.

​

I the near future I intend to use transcriptomic and DNA methylation datasets from T1D to explore the disease.

​

Past Research

My past research activities can be summarised as follows:

​

Statistical analysis of “omics” and clinical data from Type 1 diabetes: As a part of a clinical trial, I investigated drug, clinical and various immunological parameters in child patients suffering from Type 1 diabetes from Sweden using statistical methods.

​

Computational analysis of SNPs associated with human diseases:  Herein,  I have worked with SNPs of Lipopolysaccharide (LPS) binding protein (LBP), BPI, pattern recognition receptors like Toll like receptors (TLRs) and related molecules linked to sepsis, pneumonia, tuberculosis and coronary heart disease. Specifically, I used an array of computational techniques to study the role of LBP SNP (rs32232613) associated with sepsis and pneumonia; TLR1 SNP (rs4833095), TLR8 SNP (rs3764880) on susceptibility to tuberculosis and and altered reactivity to RNA; and TLR6 SNP (rs5743810) linked to coronary heart disease. In all the studies cases structural changes had a significant role in disease susceptibility. Structural analysis of the SNP in the lipopolysaccharide protein revealed a cleavage site that had limited ability to bind to LPS and lipopeptides. The TLR1 SNP revealed significant insights into structure and function in relation to tuberculosis.  The TLR8 SNP was linked to protective immunity in individuals vaccinated with BCG. The TLR6 SNP had a protective effect in healthy elderly portraying healthy ageing. All the findings from insilico studies are supported by experimental outcomes from my colleagues/collaborators.

​

Analysing Epigenetic Factors in human and Drosophila using computational tools: This included epigenomics especially targeting epigenetic factors in humans and Drosophila melanogaster using computational tools. The worked aimed at studying mechanisms of epigenetic regulation of gene expression. More specifically, my work focused on the key transcriptional memory mechanism formed by the polycomb and trithorax group proteins where I studied their targeting mechanisms using computational methods and genome-wide data sets such as ChIP-ChIP, ChIP-seq, microarray, methylation, RNA-seq and Bisulphate sequencing.

​

Investigation of the Nature of Nitrogen Fixing Microorganisms using computational approach: During my PhD, I performed computational analysis of the genomes and proteomes of nitrogen fixing microorganisms. My aim was to understand nitrogen fixing microorganisms by analysing factors affecting codon usage patterns, detecting potentially highly expressed genes and in COGs, recognising their role in effecting the lifestyle of diazotrophs; in silico proteome analysis using common physical properties and exploring the effect of isoelectric point and amino acid usages on lifestyle; re-examine molecular phylogeny of nif genes using nucleotide-triplet based condensed matrix method and homology modeling of nitrogenase iron proteins from Frankia.

​

Dissemination of Bioinformatics knowledge: During my tenure as a Research Associate in India and postdoctoral fellow in Germany I was actively engaged in training Faculty members, PhD & Master students through workshops. Moreover, I trained Faculty members in Bioinformatics tools in a Refresher Course at Vidyasagar University, India.

 

In addition to the aforesaid works, I have performed genome analysis of Frankia, Xanthomonas, Brucella, Salmonella, swine flu virus and Rhizobium phage strains. I have also performed molecular modelling and molecular dynamics simulation of pathogenesis related proteins and Frankia tRNA.