Biology subjects

Kyriacou, C.

Publications and source records attributed to Kyriacou, C..

5 recordsLinked to original sources

bioRxiv2025

Larval diapause slows adult epigenetic ageing in an insect model, Nasonia vitripennis

Epigenetic clocks based on DNA methylation provide robust biomarkers of biological age, yet the mechanistic basis and functional significance of slowing these clocks remain unclear. Progress has been limited by the lack of short-lived, genetically tractable model organisms with functional DNA methylation systems. The jewel wasp, Nasonia vitripennis, offers a unique solution. It combines a functional DNA methylation system with a short lifespan and established tools for experimental manipulation. We previously developed an epigenetic clock in Nasonia, but whether this clock reflects plastic, environmentally driven ageing processes was unknown. Here, we test this directly by experimentally inducing larval diapause, a naturally occurring developmental arrest triggered by environmental cues. Diapause extended median adult lifespan by 36% and significantly slowed the rate of epigenetic ageing. Using whole-genome bisulfite sequencing across multiple adult timepoints, we show that while adults that have passed through diapause as larvae initially emerge epigenetically older, their subsequent epigenetic ageing proceeds 29% more slowly than non-diapaused controls. Clock CpGs were enriched for gene ontology terms related to conserved nutrient-sensing and developmental pathways, including insulin/IGF signaling and mTOR, supporting the established mechanistic link between development and epigenetic ageing. These findings demonstrate that epigenetic ageing is plastic in Nasonia and can be experimentally modulated by early-life environment, establishing this animal model as a tractable system for dissecting the causal mechanisms of epigenetic ageing.

genetics↗

bioRxiv2024

Hematophagy generates a convergent genomic signature in mosquitoes and sandflies

Blood-feeding (hematophagy) is widespread across Diptera (true flies), yet the underlying molecular mechanisms remain poorly understood. Using phylogenomics, we show that four gene families associated with neuro-modulation, immune responses, embryonic development, and iron metabolism have undergone independent expansions within mosquitoes and sandflies. Our findings illuminate the underlying genetic basis for blood-feeding adaptations in these important disease vectors.

evolutionary biology↗

bioRxiv2022

The circadian clock gene bmal1 is necessary for co-ordinated circatidal rhythms in the marine isopod Eurydice pulchra (Leach).

Circadian clocks in terrestrial animals are encoded by molecular feedback loops involving the negative regulators PERIOD, TIMELESS or CRYPTOCHROME2 and positive transcription factors CLOCK and BMAL1/CYCLE. The molecular basis of circatidal ([~]12.4 hour) or other lunar-mediated cycles ([~]15 day, [~]29 day), widely expressed in coastal organisms, is unknown. Disrupting circadian clockworks does not appear to affect lunar-based rhythms suggesting a molecular independence of the two cycles. Nevertheless, pharmacological inhibition of casein kinase 1 (CK1) that targets PERIOD stability in mammals and flies, affects both circadian and circatidal phenotypes in Eurydice pulchra (Ep), the speckled sea-louse. Here we show that these drug inhibitors of CK1 also affect the phosphorylation of EpCLK and EpBMAL1 and disrupt EpCLK-BMAL1-mediated transcription in Drosophila S2 cells, revealing a potential link between the positive circadian regulators and circatidal behaviour. We therefore performed dsRNAi knockdown of Epbmal1 as well as the major negative regulator in Eurydice, Epcry2. Epcry2 and Epbmal1 knockdown disrupted Eurydices circadian phenotypes as expected but in addition, circatidal behaviour was also sensitive to Epbmal1 knockdown. Thus three Eurydice negative circadian regulators, EpCRY2, in addition to EpPER and EpTIM, do not appear to be required for the expression of circatidal behaviour, in contrast to the positive regulator EpBMAL1. We suggest a neurogenetic model whereby the positive circadian regulators BMAL1-CLK are shared between circadian and circatidal mechanisms in Eurydice but circatidal rhythms require a novel, as yet unknown negative regulator.

genetics↗

bioRxiv2021

Essential elements of radical pair magnetosensitivity in Drosophila

Many animals use the Earths magnetic field (geoMF) for navigation1. The favored mechanism for magnetosensitivity involves a blue-light (BL) activated electron transfer reaction between flavin adenine dinucleotide (FAD) and a chain of tryptophan (Trp) residues within the photoreceptor protein, CRYPTOCHROME (CRY). The spin-state of the resultant radical pair (RP), and hence the concentration of CRY in its active state, is influenced by the geoMF2. The canonical CRY-centric radical pair mechanism (RPM) does not, however, explain many physiological and behavioural observations2-8. Here, using electrophysiology and behavioural analyses, we assay magnetic field (MF) responses at single neuron and organismal level. We show that the 52 C-terminal (CT) amino acids of CRY, which are missing the canonical FAD binding domain and Trp chain, are sufficient to facilitate magnetoreception. We also show that increasing intracellular FAD potentiates both BL-induced and MF-dependent effects on the activity mediated by the CT. Additionally, high levels of FAD alone are sufficient to cause BL neuronal sensitivity and, remarkably, potentiation of this response in the co-presence of a MF. These unexpected results reveal the essential components of a primary magnetoreceptor in flies, providing strong evidence that non-canonical (i.e., non-CRY-dependent) RPs can elicit MF responses in cells.

physiology↗

bioRxiv2018

Attenuating the DNA damage response to double strand breaks is neuroprotective

DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents A{beta}1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.

neuroscience↗