A5101542121- Circadian rhythm and melatonin
- Light effects on plants
- Neurobiology and Insect Physiology Research
- Genetics, Aging, and Longevity in Model Organisms
- Plant Molecular Biology Research
- Platelet Disorders and Treatments
- Genetic diversity and population structure
- Photoreceptor and optogenetics research
- Sleep and Wakefulness Research
- Complement system in diseases
- Cell Adhesion Molecules Research
- Ophthalmology and Visual Impairment Studies
- Physiological and biochemical adaptations
- Liver physiology and pathology
- Dietary Effects on Health
- Natural product bioactivities and synthesis
- Diet and metabolism studies
- Ferroptosis and cancer prognosis
- Angiogenesis and VEGF in Cancer
- Insect behavior and control techniques
- Mechanical Circulatory Support Devices
- Spaceflight effects on biology
- Macrophage Migration Inhibitory Factor
- Genetics and Neurodevelopmental Disorders
- Lipid metabolism and disorders
University of Pennsylvania
2010-2024
Indiana University Bloomington
2018-2024
Howard Hughes Medical Institute
2005-2019
Bloomington Health Foundation
2019
Children's Hospital of Philadelphia
2005-2014
Translational Therapeutics (United States)
2013
Kunming Institute of Zoology
1999-2000
Fudan University
2000
Chinese Academy of Sciences
1999
Organisms ranging from bacteria to humans synchronize their internal clocks daily cycles of light and dark. Photic entrainment the Drosophila clock is mediated by proteasomal degradation protein TIMELESS (TIM). We have identified mutations in jetlag-a gene coding for an F-box with leucine-rich repeats-that result reduced sensitivity circadian clock. Mutant flies show rhythmic behavior constant light, phase shifts response pulses, light-dependent TIM. Expression JET along photoreceptor...
Circadian rhythms can be regulated by many environmental and endogenous factors. We show here a sensitivity of circadian clock function to oxidative stress that is revealed in flies lacking the foxo gene product. When exposed stress, wild-type showed attenuated cycling peripheral tissues, whereas mutants also lost behavioral driven central clock. FOXO expressed predominantly fat body, transgenic expression this tissue rescued mutant phenotype, suggesting has non-cell-autonomous effects on...
Sleep-wake cycles break down with age, but the causes of this degeneration are not clear. Using a Drosophila model, we addressed contribution circadian mechanisms to age-induced deterioration. We found that in old flies, free-running rhythms (behavioral assayed constant darkness) have longer period and an unstable phase before they eventually degenerate. Surprisingly, weaker light-dark circadian-regulated morning peak activity is diminished under these conditions. On molecular level, aging...
Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep autism. Although FXS the most prevalent inherited cause intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as model FXS, we showed that select expression dfmr1 in insulin-producing cells (IPCs) brain was sufficient to restore normal circadian behavior rescue memory deficits...
The pathophysiology of refractive errors is poorly understood. Myopia (nearsightedness) in particular both blurs vision and predisposes the eye to many blinding diseases during adulthood. Based on past findings diurnal variations dimensions eyes humans other vertebrates, altered rhythms these ocular with experimentally induced myopia, evolving evidence that ambient light exposures influence development, we assessed whether disturbances circadian signals might alter development eye. In mice,...
Circadian rhythms in Drosophila rely on cyclic regulation of the period (per) and timeless (tim) clock genes. The molecular cycle requires rhythmic phosphorylation PER TIM proteins, which is mediated by several kinases phosphatases such as Protein Phosphatase-2A (PP2A) Phosphatase-1 (PP1). Here, we used mass spectrometry to identify 35 "phospho-occupied" serine/threonine residues within PER, 24 are specifically regulated PP1/PP2A. We found that cell culture assays were not good predictors...
Loss of the Neurofibromatosis 1 (Nf1) protein, neurofibromin, in Drosophila disrupts circadian rhythms locomotor activity without impairing central clock function, suggesting effects downstream clock. However, relevant cellular mechanisms are not known. Leveraging discovery output circuits for rhythms, we dissected actions neurofibromin recently identified substrates. Herein, show that affects levels and cycling calcium multiple peptidergic neurons. A prominent site action is pars...
The Drosophila PAR domain protein 1 ( Pdp1 ) gene encodes a transcription factor with multiple functions. One isoform, PDP1ε, was proposed to be an essential activator of the core clock gene, Clock Clk ). However, central function for PDP1ε recently disputed, and genetic analysis has been difficult due developmental lethality -null mutants. Here we report discovery mutation that specifically disrupts ε isoform. Homozygous mutants are viable exhibit arrhythmic circadian behavior in constant...
SLOB binds to and modulates the activity of Drosophila Slowpoke (dSlo) calcium activated potassium channel. Recent microarray analyses demonstrated circadian cycling slob mRNA. We report mRNA protein expression pattern in heads. transcript is present photoreceptors, optic lobe, pars intercerebralis (PI) neurons surrounding brain cortex. exhibits a similar distribution pattern, we show that it cycles heads, photoreceptor cells neurosecretory PI. The altered various clock gene mutants,...
Circadian clocks regulate many different physiological processes and synchronize these to environmental light:dark cycles. In Drosophila, light is transmitted the clock by a circadian blue photoreceptor CRYPTOCHROME (CRY). response light, CRY promotes degradation of protein TIMELESS (TIM) then itself degraded. To identify novel genes involved in entrainment, we performed an unbiased genome-wide screen Drosophila cells using sensitive quantitative assay that measures light-induced CRY. We...
Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila melanogaster, is a critical component of the circadian clock that phosphorylates and promotes degradation PERIOD (PER) protein. However, other functions DBT regulation are not clear, part because severe reduction dbt causes preadult lethality. Here we report molecular behavioral phenotype viable dbtEY02910 loss-of-function mutant. We found protein levels dramatically reduced adult flies, majority mutant flies display arrhythmic...
Abstract The nuclear factor binding the κ light chain in B-cells (NFκB) is involved a wide range of cellular processes including development, growth, innate immunity, and sleep. However, genetic studies role specific NFκB transcription factors sleep have been limited. Drosophila fruit flies carry three genes encoding factors, Dorsal, Dorsal Immunity Factor (Dif), Relish. We previously found that loss Relish gene from fat body suppressed daily nighttime sleep, abolished infection-induced Here...