Page 25 - Biennial Report 2018-20 Jun 2021

In a pilot study, the effect of graded hypoxia on a group of 30 healthy individuals classified into
Prakriti groups has been studied using various physiological parameters such as blood pressure,
respiratory rate, heart rate, SpO2, and heart rate variability. Different biochemical parameters
such as complete blood count, fasting blood sugar, lipid profile, and Hb1AC before and after the
hypoxia exposure have been estimated. For assessing the system wide effect of hypoxia,
genome-wide expression profiling has been carried out using RNA isolated from the blood
samples of these individuals. The predominant Prakriti types exhibit differences at the cellular
levels. Preliminary experiments of characterization of eight LCL lines established from
predominant prakriti types have revealed inherent differences in cell proliferation rates. These
observations are being validated. Further, hypoxia exposure and heat shock response in these
LCL lines are being studied at transcriptome level. Development of Prakriti panels has been
initiated using deep-learning methods for classification of predominant Prakriti data for
recapitulating current knowledge and enhancing sensitivity. Exome sequencing of predominant
constitution types from diverse cohorts have provided variations that are linked to multisystem
phenotypes and disease predispositions. The effect of these variants on diverse disease
outcomes is being studied in cohorts such as the UK Biobank to study their potential
informativeness for epistatic effects. 1400 samples have been genotyped from Trisutra
consortium cohorts towards development of a molecular marker panel for classifying Prakriti
GSA arrays. Frameworks are being developed for probing the molecular mechanism of whole
formulation by integrating network medicine “trisutra” concepts with genomics approach. This
approach has provided the molecular mechanistic basis of Adathoda vasica (AV), a mono-herbal
Ayurveda formulation that is used to treat asthma. This alleviates asthma phenotypes and
associated signatures of inflammation and steroid resistance in a mouse model. The inhibitory
effect of AV extract on HIF-1A has been studied in a cellular hypoxia model using lung epithelial
cells. AV is also able to rescue cellular hypoxia induced mitochondrial dysfunction with respect
to basal respiration, ATP production, maximal respiration and morphological changes. A
connectivity map framework to establish links between the molecular pathways targeted by
Ayurveda formulations that are used to treat diverse disease has also been developed. This not
only reveals molecular links but also connects to the pathways targeted by FDA approved drugs
and pertubagens but also provides novel repurposing opportunities. A pilot study on
Cissamplous pareira has provided a link of estrogen axis through ESR1 to viral inhibition.

GENOMICS AND EPIGENOMICS IN HEALTH AND DISEASE

Genetic information is passed forward from one generation to the next through genomic DNA.
Over and beyond this genetic information, modifications on the genomic DNA in the form of
methylation can modulate the expression of genes, thus adding a layer of epigenetic information
over the genetic component. Epigenetics is now believed to be the interface of genetics and
environmental influence. For instance, maternal diet, nutrition and exposure to toxic or
addictive substances is known to affect the phenotype of the offspring. To understand the role
of vitamin B12 in epigenetic inheritance, Shantanu Sengupta’s group at IGIB has tied up with
National Institute of Nutrition, Hyderabad. The methylome and proteome of liver, kidney and
skeletal muscle of rats was characterized in three-month old male and female offspring born to
B12 deficient mothers. By comparing the methylome and proteome profile a large number of
metabolic genes were found to be differentially methylated. These changes were largely gender
specific, but correlated well with the changes in protein expression.

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