Biology subjects

Dahiya, D.

Publications and source records attributed to Dahiya, D..

4 recordsLinked to original sources

bioRxiv2025

Neuromodulation of Swarming Behavior in C. elegans: Insights into the Conserved role of Calsyntenins

Collective animal behaviors arise from a complex interplay between internal physiological states and external environmental cues. In Caenorhabditis elegans, favorable conditions promote dispersal, while stressors like food scarcity or overcrowding trigger aggregation. Here, we describe a distinct behavior termed as swarming, where C. elegans move and feed in aggregates despite abundant food availability. While environmental factors have been implicated in this behavior, the underlying genetic and molecular mechanisms remain unclear. We identify a novel role for the conserved calsyntenin protein CASY-1 in regulating swarming. Through genetic, behavioral, and optogenetic approaches, we show that CASY-1 functions in sensory neurons to modulate the neuropeptide pigment-dispersing factor (PDF) signaling. Mutants in casy-1 show impaired PDF-1 signaling and reduced inhibition of the serotonin pathway, a known regulator of social behaviors. This dysregulation, along with its associated mechanosensory and foraging defects, likely contributes to the swarming phenotype. Our findings reveal a putative neuromodulatory pathway critical for swarming behavior in C. elegans.

neuroscience↗

bioRxiv2025

Epigenetic Control of TERRA by FTSJ3 is Critical for Telomerase-Driven Cancers

Telomerase reverse transcriptase (hTERT) overexpression, a hallmark of most cancers, drives tumorigenesis by enabling limitless replicative potential. Direct targeting of hTERT is challenging, necessitating alternative strategies. Through genome-wide synthetic dosage lethality (SDL) screening in cancer models, including patient-derived organoids, we identify FTSJ3, an RNA 2-O-methyltransferase, as a critical vulnerability in hTERT-overexpressing cells. FTSJ3 methylates telomeric repeat-containing RNA (TERRA), a modification essential for recruiting SUV39H1 to telomeric ends to mediate H3K9 trimethylation and establish stable heterochromatin. Loss of FTSJ3 disrupts this cascade, impairing H3K9 trimethylation, HP1-alpha recruitment, and telomeric heterochromatin maintenance. Notably, this reveals an unexpected dependency on TERRA methylation for telomeric heterochromatin stability in hTERT-driven cancers. Non-malignant cells, lacking telomerase activity and de novo telomere repeat synthesis, are unaffected by FTSJ3 suppression. Our findings establish the FTSJ3/TERRA/SUV39H1 axis as a critical mechanism supporting telomeric heterochromatin stability in hTERT-driven cancers. This telomere-directed epigenetic strategy provides a robust framework for translational therapeutic innovation.

cancer biology↗

bioRxiv2022

A role for myeloid miR-155 in regulating hypoxia induced seizures in neonatal C57BL/J6 mice

Hypoxic ischaemic injury (HIE) in the neonatal brain has significant consequences on neurodevelopment and increases the occurrence of neurological deficits in infants. HIE is also a leading cause of neonatal seizures. Therapeutic options for the treatment of HIE are very limited. Hypoxia-ischemia directly damages brain tissue in a primary-wave of injury which activates a cascade of events triggering local and systemic inflammatory responses, driven by the innate immune system, which contribute to a significant secondary-wave of injury taking place as early as 6 hours post-hypoxia-ischaemia. Levels of the well documented inflammatory microRNA, miR-155 are elevated in rodent seizure and epilepsy models. Here, we assessed the impact of, miR-155 deletion in myeloid cells, on regulating inflammation and seizure severity in a preclinical model of neonatal hypoxia-induced seizures (Hypoxia-Sz). Wildtype miR-155 (miR-155+/+LysMCre) mice were compared to a mouse line in which miR-155 was deleted in myeloid cells (miR-155fl/fl LysMCre). We demonstrate significant upregulation of miR-155 target genes, brain-derived neurotrophic factor (bdnf), arginase-2 (arg-2), ship-1 and socs-1 in miR-155fl/fl LysMCre mice compared to controls at various time points following Hypoxia-Sz. Conversely, we report decreased mRNA levels of pro-inflammatory cytokines IL-1{beta} and IL-6 and lower protein levels of IL-1{beta} in miR-155fl/fl LysMCre mice as compared to WTs. Myeloid miR-155 deletion significantly reduced behavioural seizure severity score, reduced electrographically (EEG) measured seizure frequency and seizure burden as compared to mice to wildtypes, suggesting miR-155 regulation of seizure occurrence in this model. Behavioural tests for motor functions at 5 weeks post Hypoxia-Sz demonstrated differences between genotypes. Excitingly this work highlights that inhibition of miR-155, specifically in myeloid cells, may hold therapeutic benefit for both seizures and comorbidities associated with hypoxic brain injury.

neuroscience↗

bioRxiv2020

Germline DNA replication shapes the recombination landscape in mammals

SummaryGenetic recombination generates novel trait combinations and understanding how recombination is distributed across the genome is key to modern genetics. The PRDM9 protein defines recombination hotspots, however megabase-scale recombination patterning is independent of PRDM9. The single round of DNA replication, which precedes recombination in meiosis, may establish these patterns, therefore we devised a novel approach to study meiotic replication that includes robust and sensitive mapping of replication origins. We find that meiotic DNA replication is distinct; reduced origin firing slows replication in meiosis and a distinctive replication pattern in human males underlies the sub-telomeric increase in recombination. We detected a robust correlation between replication and both contemporary and ancestral recombination and found that replication origin density coupled with chromosome size determines the recombination potential of individual chromosomes. Our findings and methods have far-reaching implications for understanding the mechanisms underlying DNA replication, genetic recombination, and the landscape of mammalian germline variation.

genomics↗