Page 38 - CSIR-IGIB Annual Report 2020-21
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implying that  these associations maybe           worm, to identify novel factors.  One such novel
                protecting the cell from the toxic effects of CAG   factor, induced strongly  in the regenerating
                repeat  RNA. Besides SCA17, we found that         worm, was christened Neev.  Neev was
                Stat1, a key regulator of interferon  pathway     expressed in four dots per segment, at the base
                genes was induced in mouse models  of other       of each chaetae, the chitin coated projections
                polyglutamine diseases. We are  currently         that allow the worm to grip and move through
                exploring if the induction of interferon pathway   soil. In the regenerating worm, the expression
                is a common feature of multiple polyglutamine     of Neev was highest in regions where new
                disease models.  Further,  tools  for knocking    chaetae were being formed.  Sequence analysis
                down interferon expression have been              showed that it has  minimal protein coding
                developed.  The potential protective role of      potential, suggesting this was a non-coding
                knockdown of interferon signaling in the mouse    RNA. The sequence of Neev presented several
                brain will be explored in future.                 binding sites for  miRNAs, which were also
                                                                  complementary to the Chitin synthase 8 gene.
                Novel Regeneration Factors from Earthworm         We reasoned that Chitin synthase maybe
                Neurons are highly polarized with specialized     induced in only those cells that form the base of
                sub-cellular locations that make contacts with    the chaetae, and only during the formation of
                other neurons. In the adult mammalian central     new chaetae.  The lncRNA Neev, we proposed,
                nervous system, most neurons are terminally       sponges away miRNAs and allows the selective
                differentiated and barring a limited supply of    derepression of chitin synthase in the
                stem cells, there is little regenerative potential.   regenerating tissue. LncRNAs that act as miRNA
                In sharp contrast, several invertebrates  can     sponges can be expressed in a highly restricted
                regenerate  nerves following amputation.   We     pattern, ensuring spatio-temporal regulation
                initiated work on the earthworm, Eisenia fetida   during regeneration.
                to identify novel regeneration factors that may
                be responsible for the remarkable regenerative    Besides  these major  projects, a  method  for
                potential of this worm. This six-inch long, top-  miRNA profiling in patient serum was developed
                soil dwelling, vermicomposting worm, when cut     and deployed to study the differences between
                into two pieces, will regenerate the muscle, gut,   mild/ moderate and severe patients.  This
                nerve cord  and vasculature in  the  posterior    method was also used for biomarker
                region.   We carried out genome sequencing,       identification  in Downs syndrome  patients
                time dependent transcriptome analysis and         classified according  to  the severity of  neuro-
                metagenome analysis of the regenerating           developmental defects.



















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