Biology subjects

Abou Daya, F.

Publications and source records attributed to Abou Daya, F..

3 recordsLinked to original sources

bioRxiv2025

Drosophila Modeling of Insomnia-Associated Genes Reveals Diverse Underlying Sleep Phenotypes

Insomnia is a prevalent sleep disorder with highly heterogenous manifestations. While data-driven approaches to insomnia subtyping have revealed potential differences between proposed insomnia subtypes and their impacts on overall health, little is known about the genetic factors that underly and differentiate these potential insomnia subtypes. We utilize a human-genetics driven approach to Drosophila modeling to identify the range of sleep traits regulated by insomnia-associated genes. Modeling pan-neuronal loss of Drosophila orthologs of a set of insomnia genes reveals a broad range of sleep phenotypes. Through systematic characterization of traits related to sleep quantity, timing, and quality, we identify genetic factors that co-regulate aspects of the insomnia-associated phenotypic landscape. Out of the 75 insomnia-associated genes identified, only 1/3 had at least one Drosophila ortholog that regulated overall sleep quantity. In contrast, 1/3 of the insomnia-associated genes had at least one Drosophila ortholog that regulated either sleep timing or sleep quality, without impacting sleep quantity. Together this work, in Drosophila, provides support for a genetic influence on the differences between insomnia subtypes.

neuroscience↗

bioRxiv2025

Drosophila Modeling Identifies Increased Sleep as a Link Between Insomnia and Cardiovascular Disease

Insomnia is a common sleep disorder associated with negative long-term health outcomes, including cardiovascular disease (CVD). We selected 16 genes from 13 insomnia- and CVD- associated genetic loci and disrupted Drosophila melanogaster orthologs in neuronal or cardiac tissue to characterize their roles in regulating sleep and cardiac physiology. Neuronal disruption of four orthologs (APOB, FUR, CYP17A1, and TCF4) resulted in short-sleeping flies, and three (MRAS, HDAC9, and TDRKH) resulted in long-sleeping flies. Short-sleeping fly lines impacted cardiac physiology consistent with links between short or poor-quality sleep and increased CVD in humans. Conversely, heart-specific disruption of five orthologs (RASD1, PHACTR1, CNNM2, MRAS, and TCF4) led to defects in cardiac physiology, with varied effects on sleep. Heart-specific knockdown lines that altered fractional shortening, a measure of cardiac contractility, also influenced long and short sleep states. These findings reveal bidirectional relationships between sleep states and cardiac performance, representing a potential feedback loop linking insomnia and CVD.

neuroscience↗

bioRxiv2023

Identifying novel links between cardiovascular disease and insomnia by Drosophila modeling of genes from a pleiotropic GWAS locus

Insomnia symptoms have been associated with cardiovascular disease (CVD), doubling the risk of incident CVD, but specific shared pathways remain poorly understood. Recently, genome-wide association studies (GWAS) identified genetic loci significantly associated with insomnia symptoms, including one locus (near ATP5G1, UBE2Z, SNF8, IGF2BP1, and GIP) that was previously linked with CVD in an independent GWAS. To evaluate the cell-autonomous role of genes within the 17q21 insomnia and CVD locus, we used Drosophila melanogaster models to perform tissue-specific RNAi knockdown of four conserved orthologues (ATPSynC, Lsn, Bruce, and Imp) in neurons and in the heart. To identify non-cell-autonomous mechanisms, we also assessed heart function in flies with neuronal-specific knockdown and sleep in flies with heart-specific knockdown. Neuronal and cardiac-specific RNAi knockdown of several of the genes conserved in Drosophila led to compromised sleep quality and impaired cardiac performance. Neuronal-specific knockdown of ATPSynC, Imp, and Lsn led to disruptions in sleep quantity and quality. Knockdown of ATPSynC and Lsn in the heart led to significantly reduced cardiac performance without and with cardiac dilation, respectively. Furthermore, Lsn and ATPSynC-suppressed hearts showed disruption in the actin-containing myofibrillar organization and led to a significantly shortened lifespan. Non-cell-autonomous effects were seen both from neurons to heart (Imp), and heart to neurons (ATPSynC and Lsn). Specifically, Imp neuronal knockdown led to a significantly compromised cardiac function, whereas knockdown of ATPSynC and Lsn in the heart led to compromised sleep characterized by increased sleep fragmentation, both accompanied by an increase in inflammation through Upd3, an inflammatory cytokine, in the heart or head, respectively. We also demonstrate disrupted cardiac function or sleep upon cardiac-specific or neuronal-specific overexpression of Upd3, respectively, showing a direct link between cardiac dysfunction and sleep disruption through inflammation. Our study reveals tissue-specific and cross-tissue consequences of Drosophila knockdown of multiple genes at this locus, providing novel insights into potential genetic mechanisms linking CVD and insomnia. Our study also highlights the key role of these four conserved genes in both sleep and cardiac function.

physiology↗