About

Isaac Edery is a professor in the Department of Molecular Biology and Biochemistry at Rutgers University. His research focuses on studying the molecular and cellular bases underlying daily behaviors, particularly the daily changes in wake-sleep states. His work investigates how circadian clocks, sensory inputs such as light and temperature, and physiological factors like feeding and metabolic state regulate daily rhythms in wakefulness and sleep. Edery's overarching goal is to discover novel pathways that control wake-sleep states and understand how these pathways respond to environmental changes. His research employs the genetics of Drosophila, combined with biochemical, proteomic, evolutionary, cell culture, behavioral, and histochemical approaches. He has contributed to elucidating mechanisms underpinning circadian clocks, identifying novel clock genes, and demonstrating their conservation with mammalian systems, which has implications for understanding human sleep disorders. Recently, his work has shifted toward understanding sleep and arousal mechanisms using Drosophila as a model system. Notably, he discovered a new sleep-arousal gene called daywake (dyw), which encodes a hormone-binding protein and acts as an anti-siesta gene, modulated by temperature through a novel trans-splicing mechanism involving the period (per) gene. His studies also include identifying other genes regulating sleep-wake balance and integrating natural populations to provide an evolutionary perspective. His research aims to shed light on the role of sleep in health and disease, with particular interest in daytime sleep's genetic basis and its impact on learning, memory, well-being, and disease prognosis.

Research topics

• Biology
• Genetics
• Evolutionary biology
• Ecology

Selected publications

• Did a small thermosensitive intron contribute to the temperate adaptation of Drosophila melanogaster?

  Medical Research Archives · 2023 · 1 citations

  1st authorCorresponding
  • Evolutionary biology
  • Biology
  • Ecology

  and its historical journey in becoming a popular research organism.

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• <scp>DAYWAKE</scp> implicates novel roles for circulating lipid‐binding proteins as extracerebral regulators of daytime wake–sleep behavior

  FEBS Letters · 2023-12-19

  articleOpen accessSenior authorCorresponding

  Sleep during the midday, commonly referred to as siesta, is a common trait of animals that mainly sleep during the night. Work using Drosophila led to the identification of the daywake (dyw) gene, found to have anti-siesta activity. Herein, we show that the DYW protein undergoes signal peptide-dependent secretion, is present in the circulatory system, and accumulates in multiple organs, but, surprisingly, it is not detected in the brain where wake-sleep centers are located. The abundance of DYW in adult flies is regulated by age, sex, temperature, and the splicing efficiency of a nearby thermosensitive intron. We suggest that DYW regulates daytime wake-sleep balance in an indirect, extracerebral manner, via a multi-organ network that interfaces with the circulatory system.

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• Author response for "&lt;scp&gt;DAYWAKE&lt;/scp&gt; implicates novel roles for circulating lipid‐binding proteins as extracerebral regulators of daytime wake–sleep behavior"

  2023-11-29

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• Casein kinase rolls the dice in clocks from bread mold to humans

  Proceedings of the National Academy of Sciences · 2022-03-21

  letterOpen access1st authorCorresponding

  Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

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• Daywake, an Anti-siesta Gene Linked to a Splicing-Based Thermostat from an Adjoining Clock Gene

  Current Biology · 2019-05-01 · 33 citations

  articleOpen accessSenior authorCorresponding
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• The SR protein B52/SRp55 regulates splicing of the period thermosensitive intron and mid-day siesta in Drosophila

  Scientific Reports · 2018-01-24 · 18 citations

  articleOpen accessSenior authorCorresponding

  Similar to many diurnal animals, Drosophila melanogaster exhibits a mid-day siesta that is more robust as temperature increases, an adaptive response that aims to minimize the deleterious effects from exposure to heat. This temperature-dependent plasticity in mid-day sleep levels is partly based on the thermal sensitive splicing of an intron in the 3' untranslated region (UTR) of the circadian clock gene termed period (per). In this study, we evaluated a possible role for the serine/arginine-rich (SR) splicing factors in the regulation of dmpi8 splicing efficiency and mid-day siesta. Using a Drosophila cell culture assay we show that B52/SRp55 increases dmpi8 splicing efficiency, whereas other SR proteins have little to no effect. The magnitude of the stimulatory effect of B52 on dmpi8 splicing efficiency is modulated by natural variation in single nucleotide polymorphisms (SNPs) in the per 3' UTR that correlate with B52 binding levels. Down-regulating B52 expression in clock neurons increases mid-day siesta and reduces dmpi8 splicing efficiency. Our results establish a novel role for SR proteins in sleep and suggest that polymorphisms in the per 3' UTR contribute to natural variation in sleep behavior by modulating the binding efficiencies of SR proteins.

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• Parallel clinal variation in the mid-day siesta of Drosophila melanogaster implicates continent-specific targets of natural selection

  PLoS Genetics · 2018-09-04 · 19 citations

  articleOpen accessSenior authorCorresponding

  Similar to many diurnal animals, Drosophila melanogaster exhibits a mid-day siesta that is more robust as ambient temperature rises, an adaptive response aimed at minimizing exposure to heat. Mid-day siesta levels are partly regulated by the thermosensitive splicing of a small intron (termed dmpi8) found in the 3' untranslated region (UTR) of the circadian clock gene period (per). Using the well-studied D. melanogaster latitudinal cline along the eastern coast of Australia, we show that flies from temperate populations sleep less during the day compared to those from tropical regions. We identified combinations of four single nucleotide polymorphisms (SNPs) in the 3' UTR of per that yield several different haplotypes. The two most abundant of these haplotypes exhibit a reciprocal tropical-temperate distribution in relative frequency. Intriguingly, transgenic flies with the major tropical isoform manifest increased daytime sleep and reduced dmpi8 splicing compared to those carrying the temperate variant. Our results strongly suggest that for a major portion of D. melanogaster in Australia, thermal adaptation of daily sleep behavior included spatially varying selection on ancestrally derived polymorphisms in the per 3' UTR that differentially control dmpi8 splicing efficiency. Prior work showed that African flies from high altitudes manifest reduced mid-day siesta levels, indicative of parallel latitudinal and altitudinal adaptation across continents. However, geographical variation in per 3' UTR haplotypes was not observed for African flies, providing a compelling case for inter-continental variation in factors targeted by natural selection in attaining a parallel adaptation. We propose that the ability to calibrate mid-day siesta levels to better match local temperature ranges is a key adaptation contributing to the successful colonization of D. melanogaster beyond its ancestral range in the lowlands of Sub-Saharan Africa.

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• Additional file 3: Table S2. of Mid-day siesta in natural populations of D. melanogaster from Africa exhibits an altitudinal cline and is regulated by splicing of a thermosensitive intron in the period clock gene

  Figshare · 2017-01-01

  articleOpen accessSenior author

  Effect of altitude on period length in Cameroon and Kenya flies. (DOCX 15 kb)

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• Mid-day siesta in natural populations of D. melanogaster from Africa exhibits an altitudinal cline and is regulated by splicing of a thermosensitive intron in the period clock gene

  BMC Evolutionary Biology · 2017-01-23 · 20 citations

  articleOpen accessSenior authorCorresponding

  BACKGROUND: Many diurnal animals exhibit a mid-day 'siesta', generally thought to be an adaptive response aimed at minimizing exposure to heat on warm days, suggesting that in regions with cooler climates mid-day siestas might be a less prominent feature of animal behavior. Drosophila melanogaster exhibits thermal plasticity in its mid-day siesta that is partly governed by the thermosensitive splicing of the 3'-terminal intron (termed dmpi8) from the key circadian clock gene period (per). For example, decreases in temperature lead to progressively more efficient splicing, which increasingly favors activity over sleep during the mid-day. In this study we sought to determine if the adaptation of D. melanogaster from its ancestral range in the lowlands of tropical Africa to the cooler temperatures found at high altitudes involved changes in mid-day sleep behavior and/or dmpi8 splicing efficiency. RESULTS: Using natural populations of Drosophila melanogaster from different altitudes in tropical Africa we show that flies from high elevations have a reduced mid-day siesta and less consolidated sleep. We identified a single nucleotide polymorphism (SNP) in the per 3' untranslated region that has strong effects on dmpi8 splicing and mid-day sleep levels in both low and high altitude flies. Intriguingly, high altitude flies with a particular variant of this SNP exhibit increased dmpi8 splicing efficiency compared to their low altitude counterparts, consistent with reduced mid-day siesta. Thus, a boost in dmpi8 splicing efficiency appears to have played a prominent but not universal role in how African flies adapted to the cooler temperatures at high altitude. CONCLUSIONS: Our findings point towards mid-day sleep behavior as a key evolutionary target in the thermal adaptation of animals, and provide a genetic framework for investigating daytime sleep in diurnal animals which appears to be driven by mechanisms distinct from those underlying nighttime sleep.

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• Acute Dietary Restriction Acts via TOR, PP2A, and Myc Signaling to Boost Innate Immunity in Drosophila

  Cell Reports · 2017-07-01 · 40 citations

  articleOpen access

  Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A. Upregulation of Myc through genetic and pharmacological means mimicked the effects of yeast restriction in fully fed flies, identifying Myc as a pro-immune molecule. Short-term dietary or pharmacological interventions that modulate TOR-PP2A-Myc signaling may provide an effective method to enhance immunity in vulnerable human populations.

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Recent grants

• NIH Grant R56NS042088

  NIH · $386k · 2010

• Mechanisms Underlying Seasonal Adaptation of Daily Behaviors

  NIH · $1.7M · 2018–2025

• NIH Grant R01NS034958

  NIH · $6.8M · 2018

• NIH Grant R01NS042088

  NIH · $3.9M · 2015

Frequent coauthors

• Nahum Sonenberg

  McGill University

  45 shared

• Evrim Yildirim

  University of Michigan–Ann Arbor

  22 shared

• Kwang Huei Low

  Rutgers, The State University of New Jersey

  21 shared

• Joanna C. Chiu

  20 shared

• John W.B. Hershey

  15 shared

• Susan C. Milburn

  14 shared

• Michael Rosbash

  13 shared

• Douglas H. Pike

  Rutgers, The State University of New Jersey

  12 shared