Page 7 - CSIR-IGIB Annual Report 2020-21

How do complex multigene signatures contribute to systems level phenotypic signatures that define
interindividual differences? Ayurgenomics attempts to address this using the traditional knowledgebase
of population stratification based on Prakriti and the modern tools of genomics. In a team led by Bhavana
Prasher and Mitali Mukerji, these principles are being applied to asthma, COVID-19, and several other
diseases. Well characterised cohorts with detailed phenotypic analysis based on Ayurveda principles,
development of lymphoblastoid lines, animal models, system level understanding with gene expression
data and ayurveda based interventions to target altered pathways, form the basis of these studies. The
goal is to bring treatment success despite inter-individual differences. This inter-individual response to
external cues becomes critical in clinical decision making especially in case of life saving drugs with varied
outcomes. Ritushree Kukreti’s lab has been working in the area of pharmacogenomics with a focus on
epilepsy. With a panel of blood-based signatures in cases of different etiologies and drug responsiveness,
their latest study identifies the potential of COX-2 inhibitors as an adjunct therapy for poor responders
of Valproic acid.

The environment we live in contributes significantly to the outcome of genetic predispositions we are
born with. The contribution of these “external” factors with genetics is another thrust area at
IGIB. Anurag Agrawal’s lab reports on a large-scale study questioning the “normal” lung health of
residents of the country which present with low lung function compared to other global populations. He
reports that poor lung function is probably a consequence of environmental factors in addition to genetic
differences. This work was an example of large-scale health data management and analysis that is likely
to impact policy decisions. On a larger scale, Anuarg served as the co-chair of the Lancet-Financial Times
commission for governing health futures in a digital world and as a member of the WHO Technical
Advisory Group for Digital Health. Naveen Arora’s lab has been a leader in allergen research and has also
made headway in the research on diesel exhaust mediated respiratory disorders. Here, he reports on
immune responses elicited by certain cockroach allergens that could be used for intervention of allergies.
He also reports on characterization of the in-house developed mouse model of diesel exhaust exposure,
with respect to disease pathology markers and miRNA profiles. This could be a useful platform for
integrating environmental impact on lung health and its outcomes. Astha Mishra’s lab investigates the
role of altered epigenetic events and gene variations on the influence of harsh surroundings such as low
oxygen pressure. Here, she reports on the activation of CHOP mediated endoplasmic reticulum stress
and its downstream effects on pro-inflammatory gene expression under oxygen deprived conditions
using cellular models. Her lab is also developing machine learning algorithms for better risk prediction
for CVD genetic markers with environment and genotype attributes. This is a step towards making
personalized drug response predictions based on a given genotype.

Epigenetics has also been able to explain to some extent the role of diet in health outcomes. Shantanu
Sengupta’s lab has been investigating how a diet poor in Vitamin B12 impacts dislipidemia. Using human
clinical data, rat model of transgenerational vitamin B12 deficiency, and yeast as a model to study one-
carbon metabolism, he reports here lipidomic and proteomic level evidence supporting the central role
of Vitamin B12 and the balance of one-carbon metabolism in health.

Non-coding RNAs form the largest group of epigenetic modifiers that remain to be functionally
characterized. Beena Pillai’s lab, interested in epigenetic regulation in neurons, has been working on
epigenetic mode of gene regulation in neurons. Working across model systems, Beena’s lab is working
towards identifying non-coding RNAs involved in neuronal development/pathophysiology, and their
mechanisms of action. She reports on the identification of a novel non-coding RNA in regenerating
earthworms that might work as a miRNA sponge involved in regulation of chitin synthesis. Malabika
Dutta’s lab investigates epigenetic mechanisms at play in diabetes and its associated complications using

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