Omics
Diagnostic platform for neglected diseases Biology has never been a smooth road. To address the inherent complexity of biology, series of ‘omics’ technologies like genomics, proteomics, metabolomics, lipidomics etc. has came into the picture. An omics technology offers a comprehensive view of the molecules that make up a cell, tissue or organism. They are aimed primarily at the universal detection of genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in a specific biological sample in a non-targeted and non-biased manner. This can also be referred to as an advanced biology, integration of these techniques is called as system biology. Systems biology and omics experiments differ from traditional studies, which are largely hypothesis-driven. In contrast, systems biology experiments are hypothesis-generating, using holistic approaches where no hypothesis is known or prescribed but all data are acquired and analyzed to define a hypothesis that can be further tested. Omics technology can be applied not only for the greater understanding of normal physiological processes but also in disease processes where they play a role in screening, diagnosis and prognosis as well as aiding our understanding of the etiology of diseases. Our lab has explored the cutting edge omics platform in multiple facets of biology. We have state of art LC-MS facility includes TempoTM MDLC-Q-TOF (SCIEX) and Agilent Triple Quad LC-MS. Genomics To understand the biology and evolution of pathogens, we rely on an array of high throughput omics technologies. Research based on whole genome sequencing of pathogens not only enables understanding of fundamental science but also helps in the clinical management of infectious disease. We have resequenced the genome of Giardia lamblia, a protozoan parasite and uncovered unique trans splicing of genes in this early branching eukaryote. (Nageshanet. al., J BiolChem. 2011 Mar 4;286(9):7116-22). Currently we are trying to understand mechanisms of trans splicing. We have also generated the first draft genome of a multidrug resistant fungal pathogen called Candida auris which is now the reference genome in the world. C. auris infections were routinely misdiagnosed as C. haemulonii in clinical settings. The whole genome sequence has guided us not only to find virulence determinants of the pathogen, but also aided in the discovery of novel markers to differentiate between related species, thereby providing a specific solution to the diagnostic dilemma. (Chatterjee Set.al., BMC Genomics. 2015 Sep 7;16(1):686) Proteomics Proteins are the workhorses in an organism. Proteins are not only a reflection of the genome and transcriptome of the organism but are modulated at different stages and under different conditions. The proteome (a collection of all proteins expressed at a given time and under given conditions) of an organism is highly dynamic; chemical modifications, subcellular localization of the protein and environmental conditions can all modulate the expression and activity of proteins. In the lab, we employ methods like two-dimensional gel electrophoresis (2D-GE), differential gel electrophoresis (DIGE) and the highly sensitive liquid chromatography-mass spectrometry (LC-MS) to study the proteome of different parasitic organisms which include Plasmodium, Giardia, Trichomonas, Candida and Cryptococcus. These tools facilitate our understanding of the dynamic nature of the proteomes of these organisms under different treatment regimens. Our lab was among the first to publish the clinical proteome of Plasmodium falciparum and Plasmodium vivax. We also employ these tools to analyze post translational modifications in the proteins of these organisms. Apart from looking at the global proteome, the lab is also focused on chaperone proteins, mainly heat shock protein 90 (Hsp90). Our studies revealed that Hsp90 level is critically important in survival and stage transition in various parasites and Hsp90 inhibitors could serve as efficient anti-parasitic drugs. Metabolomics Metabolomics is a newest omics approach used by researchers. It is often referred to as the last piece of puzzle in the OMICS group. It represents the entire repertoire of small molecules in an organism. Metabolomics, along with other omics applications, provides a holistic understanding of the functioning of the organism. Themetabolome of the organism is closely linked to its phenotype and thus forms an important tool in disease biology. We currently use Mass Spectrometry based analysis of malaria-infected patients’ serum to identify unique malaria-specific biomarkers. We also employ a quantitative targeted as well as untargeted approach to decipher the metabolic pathways in the parasite. We use the same approach to identify in-born errors of metabolism in neonates. These disorders constitute a diverse heterogenous group of disorders and a significant percentage of neonates suffer from these disorders. Early detection by using the highly sensitive method of mass spectrometry could potentially helps in early diagnosis and accurate treatment for children suffering from these diseases.