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ELUCIDATING THE ROLE OF WNT INDUCED SECRETED PROTEIN 3(WISP3) IN MITOCHONDRIAL FUNCTION
Full text linkStudies on Contribution of Astrocyte Secreted Proteins on Neuronal Health in Models of Alzheimer’s Disease
Full text linkElucidation of Relationship between Glutathione and Plant Defense in Arabidopsis thaliana
Full text linkUnderstanding the mechanism of cardiac gene remodelling via PPAR-α signalling in cardiac hypertrophy
Full text linkidentified and unveiled the functional relevance of differentially
expressed miRNAs in ISO-treated PPAR α-/- mice. As of now, limited literature was
available about miRNA abundance and their altered expression in cardiac hypertrophy
models in the absence of PPAR α protein. So for the very first time, using PPAR α-/- mice,
we showed that several miRNAs are differentially expressed that have never been reported in
context to cardiac hypertrophy. Additionally, pathway analysis, indicated that the
dysregulated miRNAs target genes were enriched mostly in signal transduction pathways.
Overall, our findings suggest the miRNAs expression profile of miRNAs like mmu-miR3102-5p; mmu-miR-30a-5p; mmu-miR-30c-5p; mmu-miR-466i-5p is significantly altered in
response to cardiac hypertrophy in PPAR-/- mice that eventually impacts the apoptotic
pathway in a negative manner
Understanding the Pathophysiological Implications of Dysregulated Cholesterol Homeostasis due to Altered Efflux Dynamics
Full text linkCharacterization Of Key Parasite And Host Derived Factors As Potential Immune Modulators And Their Role In Regulating Macrophage Plasticity During Murine Visceral Leishmaniasis
Full text linkRole of Cellular Membranes in Controlling Micro RNA Mediated Co-ordinated Gene Expression
Full text linkMicroRNAs are ~22 nt. regulatory RNAs that bind to 3’ UTR of target mRNA and
regulate the expression by translational repression or transcriptional inactivation. Previously
it has been reported there exists a target mRNA dependent miRNA biogenesis where target
mRNA could regulate its cognate miRNA biogenesis by modulating Dicer processivity. It is
well known that multiple miRNAs share the common 3’ UTR of the same target mRNA. So I
was curious to check the additive level of regulation in “target mRNA dependent miRNA
biogenesis” on other miRNAs that share binding sites on the same 3`UTR of target mRNA.
My aim was to dissect the molecular manifestation of this “cooperative regulation” and its
relevance in normal cellular physiology. Earlier It was observed there exists a target mRNA
dependent miRNA biogenesis where one target mRNA could regulate its cognate miRNA
biogenesis by modulating Dicer processivity. I was curious how this phenomenon affects
biogenesis of other miRNAs on the same 3`UTR. I could observe miRNA family with a
higher number of binding sites (miRNA 1) influences the biogenesis of adjacent groups of
miRNAs (miRNA 2) that shares the common 3’ UTR. Along with, I could also observe
repression of secondary mRNAs (mRNA B) that bear sites for miRNA2 (but not for
miRNA1) is co-ordinately regulated with miRNA1 abundance inside the cells.
Using a reporter based model in endotoxin-stress induced TLR4-activation module,
corroborate my findings to propose “target dependent cooperative biogenesis of miRNAs' '
phenomenon inside the mammalian cells. A computational module was developed to predict
regulatory miRNA and their network under different physiological contexts. Interestingly
again, many of those predicted cooperative miRNAs and its’ secondary target has been
revalidated biochemically that exhibits the same trend, strengthening the proposed
hypothesis. I could observe coordinated regulation of miRNAs resulting in alleviating
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bacterial endotoxin-induced pro-inflammatory response. My observations suggest "target
dependent cooperative biogenesis of miRNAs (TDCB)” added an additional layer of finetuning of signalling molecules on endotoxin-responsive murine macrophages to re-establish
cellular homeostasis. Additionally I have also shown mechanistically co-operative biogenesis
of miRNAs on macrophages play an important role to combat pro-inflammatory response.
Along with I have also explored the cellular compartmentalization of this phenomenon.
Previous reports suggest polysome attached with rER serves as the nucleation site for miRNP
assembly and miRNA mediated target mRNA repression. Here, I have observed the
differential compartmentalization of miRNAs and target mRNAs regulated by target
dependent cooperative biogenesis on those cellular compartments.
The other part of work has been concentrated on the study on importance of cellular
membranes on miRNA biogenesis and rER targeting of target mRNA and how this influences
the fate of miRNA. There I have observed reduced compartmentalization of de novo formed
miRNAs on rER or polysomes in defective mitochondria containing cells along with
increased retention of its target mRNAs. I have also observed defective target mRNA
dependent cognate miRNA biogenesis in an amino acid starved and refed hepatic cells.
Increased retention of microsomal target mRNAs in mitochondria-ER detethered cells due to
impaired recycling of miRNP components has been also observed in Mfn2 negative cells.
I have also found a defective intracellular trafficking in growth retarded senescent
mammalian cells having impaired mitochondrial potential and dynamics. Similar to what
happens in senescent cells, Uncoupling Protein 2 mediated depolarization of mitochondrial
membrane potential results in progressive sequestration of miRNAs with polysomes.
Mitochondrial detethering of endoplasmic reticulum, a phenomenon also evident in
mitochondria depolarized cells, found to be responsible for defective compartmentalization of
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translation initiation factor eIF4E to ER attached polysomes. It causes retarded translation
process accompanied by enhanced retention of miRNAs and target mRNAs with rER
attached polysomes that resulted in reduced intracellular trafficking. In subsequent
experiments I have identified a reduced activity of mTORC1 in mitochondria defective cells
to cause reduced phosphorylation of eIF4E-BP1 on microsomes to cause retarded eIF-4E
targeting to ER attached polysome. Cumulatively, these data suggest intricate involvement of
mitochondrial membrane potential and dynamics to determine stability of miRNAs in
mammalian cells by affecting subcellular locations and export of miRNPs. These data
suggest how mitochondrial membrane potential and dynamics, by targeting mTORC1 activity
and compartmentalization, determine subcellular localization of miRNPs. This infers
mitochondrial detethering of rER may directly cause lowering of miRNA turnover by
targeting the initiation phase of translation caused by poor shuttling of cap binding protein
eIF4E from cytoplasmic pool to the rER associated domain
Understanding The Role Of Metabolite/Growth Factor Mediated Bioenergetic And Metabolic Alterations In Tumor Cell That Facilitate Cancer Progression And Chemoresistance
Full text linkMOLECULAR ANALYSIS OF DENGUE VIRUS SEROTYPES AND CHARACTERIZATION OF THE MAJOR VIRAL NON-STRUCTURAL PROTEIN 1 (NS1) IN CELL CULTURE
Full text linkMultifunctional behavior of bis-acylhydrazone: Real-time detection of moisture in organic solvents, halochromism and aggregation induced emission
No full textA versatile novel indenopyrazine/indenoquinoxaline appended acylhydrazones (1 and 2) have been designed and synthesized successfully. Compounds 1 and 2 are designed such that, it comprises of acylhydrazone, which is responsible for moisture detection via deprotonation of the original molecule, pyrazine, pyridine and hydrazone unit which is responsible for halochromism via protonation and deprotonation, further the integrated twisted molecular structure results in the aggregation-induced emission features. Successive treatment of Fˉ and moisture to compound 1 and 2 produce reversible colorimetric responses that are easily visualized by the naked eye. Further, the corresponding mechanism was effectively confirmed by 1H NMR spectral analysis. The inherent halochromic features of appended unique pyrazine and pyridine core in compounds 1 and 2 were studied by the sequential addition of trifluoroacetic acid (TFA) and triethylamine (TEA) which is authenticated by reversible colorimetric changes as well as absorption spectral studies. Compound 1 adopts a twisted scissor-like structure and due to multiple weak interactions results in an interesting supramolecular network. Furthermore, both compound 1 and 2 exhibits the aggregation-induced emission features in DMF/water mixture, which was expansively confirmed through DLS particle analysis and TEM images. The integration of three distinct features into a single molecule are scarce