Page 65 - Biennial Report 2018-20 Jun 2021

Firstly, the status of chromatin marks at the Kalirn promoter was monitored in Zebrafish and it
was found that the Durga induced Kalirn expression was accompanied by deposition of activation
marks. The activation marks, H3K27ac and H3K4me3 were found to be increased by 8-fold and
35 fold, respectively. This favours a model wherein, Durga RNA may recruit yet unknown histone
modifier proteins to the Kalirn promoter. The possibility of localization of Durga lncRNA and
Kalirn mRNA to the synaptosomes was
also explored, where their association with
the local polyribosome
machinery may facilitate the re-
modelling of synapses. A
biotinylated version of Durga lncRNA was
used to pull-down interacting proteins
in the cell lysate from zebrafish adult
brain and found a number of
synaptosomal proteins using
proteomics in the co- immuno-precipitate,
implying a role in the synapse. The
synaptosomal proteins detected in
the RNA associated fraction included
microtubule associated protein
1Ab, neurofilament- medium polypeptide
a, calcium/calmodulin
dependent protein kinase (CaM kinase)
II gamma 1, syntaxin- binding protein 1a
and synaptotagmin VIIa. WD repeat
domain 37, a transcriptional
protein was also found in the immunoprecipitated fraction. These findings are being validated
through replicates and orthogonal methods. Reconciling both these lines of evidence, a working
model has been formulated, wherein the Durga lncRNA may play a dual role: a transcription
regulator in the nucleus and a synapse remodeling role at the synaptosome.

IDENTIFICATION SPECIFIC BIOMARKERS OF OSTEOARTHRITIS USING

PHOSPHOPROTEOMICS APPROACH

Osteoarthritis (OA) is a highly prevalent joint disease characterised by the loss of cartilage,
causing disability and loss of function and has no reliable biomarkers currently for this disease.
Till date the pathogenic mechanism underlying OA remains unclear. As the recent emergence
of new technologies, such as proteomics-based approaches provides the potential markers for
detection of a disease, Dr Sagarika’s group made an attempt to identify disease-associated
differential proteins using phosphoproteomic approach.They recruited OA patients, collected
blood, synovial fluid and tissue samples from OA patients (n=30), at the age group of 50-70 years
in collaboration with Orthopeadic Department, All India Institute of Medical Sciences (AIIMS),
New Delhi. Necessary ethical approval approved by the Human Ethics Committee of CSIR-IGIB,
and Department of Orthopaedics, AIIMS, New Delhi, India was taken. Healthy control (n=25)
blood samples were collected from individual with no history of joint symptoms. A detailed

64