Page 87 - Annual report 2021-22

Annual Report 2021-22 |

Sagarika Biswas

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Sagarika Biswas works towards developing molecular markers of joint diseases.

It has been long speculated that plant miRNAs may be transferred to primary consumers along the
food chain. However, it is not entirely clear if these plant derived miRNAs could be acquired in intact
form and could influence the target genes in the animal. Since the miRNA machinery is comparable, it
is interesting to speculate that plant derived miRNAs could affect animal species through this route.
It may even be useful and commercially relevant besides being fundamentally important. Detection
of a miRNA from the turmeric plant (C. longa miRNA; clo-mir-14) in human sera and synovial tissues
of RA and comparing its abundance in host was proposed. Screening of proteins affected by in vitro
transfection of clo-mir-14 in RA primary cells would also shed light on its functional role. Clo-mir-14
was detected in arthritis patients' serum/plasma and confirmed using RT-PCR. Stability of miRNA over
cooking temperature which is crucial for cross kingdom regulation from food source was also
established. The results indicated that the plant miRNA is stable enough to evade cooking
temperature. Primary cell line has been developed from the patients biopsy synovium and upon
induction of clo-mir-14 there is significant decrease in the level of RA specific cytokines such as TNF
alpha and IL-1beta in primary synovial cells.
Rheumatoid Arthritis (RA) is a chronic, autoimmune and progressive inflammatory joint disease.
Currently rheumatoid factor (RF), Anti-cyclic citrullinated peptide (anti-CCP), anti-citrullinated protein
antibodies (ACPA), C-reactive protein (CRP) are used for clinical diagnosis of RA. But the specificity and
sensitivity are lacking in these markers. A combined metabolome and proteome profiling to develop
a predictive biomarker set for rheumatoid arthritis assessment is being generated in the laboratory of
Sagarika Biswas. This will serve to enhance our understanding of the metabolomic profile in the
biofluids (plasma, synovial fluid and synovium) in the context of Rheumatoid arthritis along with
differential proteome profile. The aim is to understand the altered metabolites and their functional
implication in RA-Fibroblast like Synoviocytes and elucidate their association in pathogenesis.
Validation of identified metabolites and proteins in the cohort of RA patients to identify biomarker
signature and therapeutic targets will also be taken up.
High throughput analytical techniques were used in Sagarika’s lab to explore the vital modifications at
cellular level. They collected blood samples from an RA patient (n=35) and healthy (n=10) from AIIMS,
New Delhi. Metabolomic analysis of RA (n=6) and healthy (n=6) were carried out using HPLC/LCMS
followed by UPLC-HRMS technique. Pathway prediction analysis of all altered metabolites were
carried out. Significant metabolites fell under the sphingolipid and glycerophospholipid metabolism
pathway. Pooled RA and healthy samples were subjected to SWATH-MS Acquisition Using High-
Resolution Mass Spectrometry. Total 296 proteins, amongst which 197 proteins were differentially
regulated; 67 were upregulated and 129 were downregulated. Among them 29 were upregulated and
34 were downregulated.

Towards understanding differences in the patterns of osteoarthritis in the Indian and western
population, impact on symptoms, treatment options and their outcome were studied. Blood/synovial
fluid (SF)/synovium samples from 87 TKR/UKR Osteo Arthritis (OA) patients from AIIMS New Delhi and