MEDICAL BIOTECHNOLOGY / Recombinant Diagnostics and Vaccines
Tuberculosis, Proteomics, Metabolomics, volatile organic compounds (VOCs), eNOSE.
Description of Research
Tuberculosis perturbs miRNAome, proteome and metabolome of human body fluids
Global profiling of genes, proteins and metabolites using complementary OMICS platforms portrays the footprint and signatures of normal physiology as well as perturbed states of an organism. By this approach an atlas of pattern recognition representing specific and nonspecific condition of different variability can be established at population level. Combined effort of molecular details at separate hierarchical levels could help to put the pieces of puzzle together to elucidate their role to explain variability at population levels to explain the bigger picture in relation to normal and diseased conditions. These complementary techniques can be employed to discover bio-signature for various purposes like disease diagnosis and monitoring therapeutic outcomes as well as to gain understanding host pathogen relationship in tuberculosis (TB) patients.
Expression, regulation and dynamics of biofluid miRNAome, proteome and metabolome are influenced by cell processes and perturbed by external factors like infection in a steady state. Therepetuic interventions also affect fluid state of biofluid molecular constituents inside the body to sum the effect on different cell and tissue types. With the advancement of quantitative proteomics, metabolomics tools like mass spectrometry and microarray techniques it is possible to compare multiple study groups representing different stages of disease progression or treatment response to discover stage specific bio-signature. Our focus is to identify panels of marker molecules from different biological fluids like saliva, serum and urine of active TB patients recruited from our collaborative clinical sites. Molecules showing significant up or down regulations in TB patients will be identified as putative marker molecules and their specificity to TB will be established using other similar respiratory disease states (e.g. pneumonia, lung cancer). In addition we are also attempting to elucidate the role of identified altered marker molecules from different bio-fluids in host pathogen interactions using a systems biology approach.
eNOSE for early Tuberculosis diagnosis
A non-invasive method of TB diagnosis using either urine and/or breath volatile organic compounds (VOCs) biomarkers is a major focus. Our earlier findings showed that a molecular signature of six VOCs identified from urine head space could diagnose TB with high sensitivity using gas chromatography and mass spectroscopy. Similarly a signature of seven molecules was identified from the breath of TB patients with high discriminatory power. We have also observed alterations in abundance of these VOCs during anti-TB therapeutic interventions. Preliminary results on breath VOCs showed drug resistance in pulmonary TB patients, active drug curable TB patients, lung cancer and COPD patients cluster separately.
With support from Bill and Melinda Gates Foundation and Grand Challenges Canada our present focus is to validate those signatures and to identify novel marker molecules in a longitudinal study including diverse study populations. Presently we are collaborating with six clinical sites representing diverse locations in India. After careful validation of the marker molecules, partnering with Next Dimensional Technologies, USA we are exploring the possibility of developing an easy to use eNOSE as a point of care TB diagnosis method by developing sensor arrays and integrating them with decision making algorithm.
Das, M.K., Bishwal, S.C., Das, A., Dabral, D., Badireddy, V.K., Pandit, B., Varghese, G.M., Nanda RK. 2015. Deregulated tyrosine-phenylalanine metabolism in pulmonary tuberculosis patients. J Proteome Res. 14: 1947-1956. PubMed link
Das, M.K., Bishwal, S.C., Das, A., Dabral, D., Varshney, A., Badireddy, V.K., Nanda, R. 2014. Investigation of Gender-Specific Exhaled Breath Volatome in Humans by GCxGC-TOF-MS. Anal Chem 86: 1229-1237. PubMed link
Sethi, S., Nanda, R., Chakraborty T. 2013. Clinical application of Volatile Organic Compounds as Potential Biomarkers for Infections. Clin Microbiol Rev 26: 462-475. PubMed link
Subramaniam, S., Thakur, R.K., Yadav, V.K., Nanda, R., Chowdhury, S., Agrawal, A. 2013. Lung cancer biomarkers: State of the art. Journal of Carcinogenesis. 12: 3. PubMed link
Banday, K.M., Pasikanti, K.K., Chan, E.C.Y., Singla, R., Rao, K.V.S., Chauhan, V.S., Nanda, R.K. 2011. Use of urine volatile organic compounds to discriminate tuberculosis patients from healthy subjects. Anal Chem. 83: 5526- 5534. PubMed link