https://libjncir.jncasr.ac.in/xmlui/handle/10572/1534 2026-04-04T05:31:57Z https://libjncir.jncasr.ac.in/xmlui/handle/123456789/3272 Pooled-sequencing raw data for GATE populations Ghosh, Arijit 2022-07-01T00:00:00Z https://libjncir.jncasr.ac.in/xmlui/handle/123456789/3251 HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in a Drosophila model of Huntington's Disease Prakash, Pavitra; Kumar Pradhan, Arpit; Sheeba, Vasu Circadian disturbances are early features of neurodegenerative diseases, including Huntington’s Disease (HD). Emerging evidence suggests that circadian decline feeds into neurodegenerative symptoms, exacerbating them. Therefore, we asked whether known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in a Drosophila circadian HD model. The molecular chaperones HSP40 and HSP70 (Heat Shock Protein) emerged as significant suppressors in the circadian context, with HSP40 being the more potent mitigator. Upon HSP40 overexpression in the Drosophila circadian ventrolateral neurons (LNv), the behavioural rescue was associated with neuronal rescue of loss of circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment Dispersing Factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence implicating the neuroprotective chaperone HSP40 in circadian rehabilitation. The involvement of molecular chaperones in circadian maintenance has broader therapeutic implications for neurodegenerative diseases. This study shows, for the first time, a neuroprotective role of chaperone HSP40 in suppressing circadian dysfunction associated with Huntington’s Disease in a Drosophila model. 2022-05-30T00:00:00Z https://libjncir.jncasr.ac.in/xmlui/handle/10572/2291 dTRPA1 in Non-circadian Neurons Modulates Temperature-dependent Rhythmic Activity in Drosophila melanogaster Das, Antara; Holmes, Todd C.; Vasu, Sheeba In fruit flies Drosophila melanogaster, environmental cycles of light and temperature are known to influence behavioral rhythms through dedicated sensory receptors. But the thermosensory pathways and molecular receptors by which thermal cycles modulate locomotor activity rhythms remain unclear. Here, we report that neurons expressing warmth-activated ion channel Drosophila Transient Receptor Potential-A1 (dTRPA1) modulate distinct aspects of the rhythmic activity/rest rhythm in a light-dependent manner. Under light/dark (LD) cycles paired with constantly warm ambient conditions, flies deficient in dTRPA1 expression are unable to phase morning and evening activity bouts appropriately. Correspondingly, we show that electrical activity of a few neurons targeted by the dTRPA1(SH)-GAL4 driver modulates temperature-dependent phasing of activity/rest rhythm under LD cycles. The expression of dTRPA1 also affects behavior responses to temperature cycles combined with constant dark (DD) or light (LL) conditions. We demonstrate that the mid-day "siesta" exhibited by flies under temperature cycles in DD is dependent on dTRPA1 expression in a small number of neurons that include thermosensory anterior cell neurons. Although a small subset of circadian pacemaker neurons may express dTRPA1, we show that CRY-negative dTRPA1(SH)-GAL4 driven neurons are critical for the suppression of mid-thermophase activity, thus enabling flies to exhibit siesta. In contrast to temperature cycles in DD, under LL, dTRPA1 is not required for exhibiting siesta but is important for phasing of evening peak. Our studies show that activity/rest rhythms are modulated in a temperature-dependent manner via signals from dTRPA1(SH)-GAL4 driven neurons. Taken together, these results emphasize the differential influence of thermoreceptors on rhythmic behavior in fruit flies in coordination with light inputs. Restricted Access 2016-01-01T00:00:00Z https://libjncir.jncasr.ac.in/xmlui/handle/10572/1942 NMR-based investigation of the Drosophila melanogaster metabolome under the influence of daily cycles of light and temperature Gogna, Navdeep; Singh, Viveka Jagdish; Sheeba, Vasu; Dorai, Kavita We utilized an NMR-based metabolomic approach to profile the metabolites in Drosophila melanogaster that cycle with a daily rhythm. H-1 1D and 2D NMR experiments were performed on whole-body extracts sampled from flies that experienced strong time cues in the form of both light and temperature cycles. Multivariate and univariate statistical analysis was used to identify those metabolites whose concentrations oscillate diurnally. We compared metabolite levels at two time points twelve hours apart, one close to the end of the day and the other close to the end of the night, and identified metabolites that differed significantly in their relative concentrations. We were able to identify 14 such metabolites whose concentrations differed significantly between the two time points. The concentrations of metabolites such as sterols, fatty acids, amino acids such as leucine, valine, isoleucine, alanine and lysine as well as other metabolites such as creatine, glucose, AMP and NAD were higher close to the end of the night, whereas the levels of lactic acid, and a few amino acids such as histidine and tryptophan were higher close to the end of the day. We compared signal intensities across 12 equally spaced time points for these 14 metabolites, in order to profile the changes in their levels across the day, since the NMR metabolite peak intensity is directly proportional to its molar concentration. Through this report we establish NMR-based metabolomics combined with multivariate statistical analysis as a useful method for future studies on the interactions between circadian clocks and metabolic processes. Restricted access 2015-01-01T00:00:00Z