Amita Sehgal

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi Molecular genetic analysis of circadian rhythms in vertebrates and invertebrates
    A Sehgal
    Department of Neuroscience, University of Pennsylvania Medical Center, Philadelphia 19104, USA
    Curr Opin Neurobiol 5:824-31. 1995
  2. ncbi Circadian control of eclosion: interaction between a central and peripheral clock in Drosophila melanogaster
    Edith M Myers
    The Department of Neuroscience, 232 Stemmler Hall, University of Pennsylvania, Philadelphia, PA 19104, USA
    Curr Biol 13:526-33. 2003
  3. pmc Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
    Wenyu Luo
    Cell and Molecular Biology Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    Aging Cell 11:428-38. 2012
  4. pmc The central clock neurons regulate lipid storage in Drosophila
    Justin R DiAngelo
    Department of Neuroscience, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e19921. 2011
  5. pmc Cooperative interaction between phosphorylation sites on PERIOD maintains circadian period in Drosophila
    David S Garbe
    Department of Neuroscience, University of Pennsylvania School of Medicine, Translational Research Center, Philadelphia, Pennsylvania, United States of America
    PLoS Genet 9:e1003749. 2013
  6. pmc Genetics of sleep and sleep disorders
    Amita Sehgal
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 146:194-207. 2011
  7. doi Ac-ing the clock
    Amita Sehgal
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Neuron 57:8-10. 2008
  8. pmc SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker
    Mark N Wu
    Division of Sleep Medicine, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Neurosci 13:69-75. 2010
  9. pmc Identification of a neural circuit that underlies the effects of octopamine on sleep:wake behavior
    Amanda Crocker
    Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Neuron 65:670-81. 2010
  10. ncbi Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A
    Sriram Sathyanarayanan
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 116:603-15. 2004

Research Grants

  1. Cycling of Circadian Rhythm Proteins
    Amita Sehgal; Fiscal Year: 2009
  2. Cycling of Circadium Rhythm Proteins
    Amita Sehgal; Fiscal Year: 2006
  3. Cycling of Circadian Rhythm Proteins
    Amita Sehgal; Fiscal Year: 2007

Collaborators

Detail Information

Publications78

  1. ncbi Molecular genetic analysis of circadian rhythms in vertebrates and invertebrates
    A Sehgal
    Department of Neuroscience, University of Pennsylvania Medical Center, Philadelphia 19104, USA
    Curr Opin Neurobiol 5:824-31. 1995
    ..A combination of genetic, molecular and biochemical approaches is leading to an emerging picture of how molecular events enable organisms to keep time...
  2. ncbi Circadian control of eclosion: interaction between a central and peripheral clock in Drosophila melanogaster
    Edith M Myers
    The Department of Neuroscience, 232 Stemmler Hall, University of Pennsylvania, Philadelphia, PA 19104, USA
    Curr Biol 13:526-33. 2003
    ..This is the first report of a peripheral clock necessary for a circadian event...
  3. pmc Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations
    Wenyu Luo
    Cell and Molecular Biology Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
    Aging Cell 11:428-38. 2012
    ..Our data demonstrate that a robust molecular timekeeping mechanism persists in the central pacemaker of aged flies, and reducing PKA can strengthen behavioral rhythms...
  4. pmc The central clock neurons regulate lipid storage in Drosophila
    Justin R DiAngelo
    Department of Neuroscience, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 6:e19921. 2011
    ..These data demonstrate that the activity of the central clock neurons is necessary for proper lipid storage...
  5. pmc Cooperative interaction between phosphorylation sites on PERIOD maintains circadian period in Drosophila
    David S Garbe
    Department of Neuroscience, University of Pennsylvania School of Medicine, Translational Research Center, Philadelphia, Pennsylvania, United States of America
    PLoS Genet 9:e1003749. 2013
    ....
  6. pmc Genetics of sleep and sleep disorders
    Amita Sehgal
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 146:194-207. 2011
    ..To conclude, we discuss how these different strategies will be critical to unambiguously defining the function of sleep...
  7. doi Ac-ing the clock
    Amita Sehgal
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Neuron 57:8-10. 2008
    ..Degradation of these proteins usually involves ubiquitylation or sumoylation, and some of the relevant E3 ligases are known. In addition, Hirayama et al. recently identified acetylation as a clock regulatory mechanism...
  8. pmc SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker
    Mark N Wu
    Division of Sleep Medicine, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Nat Neurosci 13:69-75. 2010
    ..SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules...
  9. pmc Identification of a neural circuit that underlies the effects of octopamine on sleep:wake behavior
    Amanda Crocker
    Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Neuron 65:670-81. 2010
    ..These studies define the cellular and molecular basis of octopamine action and suggest that the PI is a sleep:wake-regulating neuroendocrine structure like the mammalian hypothalamus...
  10. ncbi Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A
    Sriram Sathyanarayanan
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 116:603-15. 2004
    ..PP2A also affects PER phosphorylation in vitro and in vivo. We propose that the posttranslational mechanisms that drive cycling of PER require the rhythmic expression of PP2A...
  11. pmc Regulation of feeding and metabolism by neuronal and peripheral clocks in Drosophila
    Kanyan Xu
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell Metab 8:289-300. 2008
    ..We propose that the input of neuronal clocks and clocks in metabolic tissues is coordinated to provide effective energy homeostasis...
  12. pmc Identification of SLEEPLESS, a sleep-promoting factor
    Kyunghee Koh
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 321:372-6. 2008
    ..Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability...
  13. pmc An isoform-specific mutant reveals a role of PDP1 epsilon in the circadian oscillator
    Xiangzhong Zheng
    Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 29:10920-7. 2009
    ..Together, these data support a model in which PDP1epsilon functions in the central circadian oscillator as well as in the output pathway...
  14. pmc FOXO and insulin signaling regulate sensitivity of the circadian clock to oxidative stress
    Xiangzhong Zheng
    Howard Hughes Medical Institute and Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 104:15899-904. 2007
    ..Together these data demonstrate that metabolism affects central clock function and provide a link among insulin signaling, oxidative stress, aging, and circadian rhythms...
  15. pmc Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1)
    Yanshan Fang
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 21:1506-18. 2007
    ..We propose a modified model for post-translational regulation of the Drosophila clock, in which PP1 is critical for the rhythmic abundance of TIM/PER while PP2A also regulates the nuclear translocation of TIM/PER...
  16. ncbi Novel insights into the regulation of the timeless protein
    Lesley J Ashmore
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 23:7810-9. 2003
    ..We propose that TIM drives cycles of PER expression by regulating its stability, and in turn, PER retains TIM in the nucleus, either for the regulation of its own stability or for a novel nuclear role of TIM...
  17. ncbi Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster
    Joan C Hendricks
    Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Biol Rhythms 18:12-25. 2003
    ..Finally, the cyc01 mutation shortened the life span of male flies. These data indicate that cycle regulates rest and life span in male Drosophila...
  18. pmc Regulation of circadian behavioral output via a MicroRNA-JAK/STAT circuit
    Wenyu Luo
    Cell and Molecular Biology Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 148:765-79. 2012
    ..In addition, central clock neurons project in the vicinity of Upd-expressing neurons, providing a possible physical connection by which the central clock could regulate JAK/STAT signaling to control rest:activity rhythms...
  19. pmc Post-translational regulation and nuclear entry of TIMELESS and PERIOD are affected in new timeless mutant
    Taichi Hara
    HHMI, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 31:9982-90. 2011
    ..We also show that a stable form of PER is cytoplasmic in tim-null flies. These studies establish an essential role of TIM in the timed nuclear entry of PER...
  20. pmc Pattern of distribution and cycling of SLOB, Slowpoke channel binding protein, in Drosophila
    Angela M Jaramillo
    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    BMC Neurosci 5:3. 2004
    ..SLOB binds to and modulates the activity of the Drosophila Slowpoke (dSlo) calcium activated potassium channel. Recent microarray analyses demonstrated circadian cycling of slob mRNA...
  21. ncbi Serotonin modulates circadian entrainment in Drosophila
    Quan Yuan
    Howard Hughes Medical Institute, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Neuron 47:115-27. 2005
    ..These data identify a molecular connection between serotonin signaling and the central clock component TIM and suggest a homeostatic mechanism for the regulation of circadian photosensitivity in Drosophila...
  22. pmc JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS
    Kyunghee Koh
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 312:1809-12. 2006
    ..Our results suggest that JET is essential for resetting the clock by transmitting light signals from CRY to TIM...
  23. pmc A genetic screen for sleep and circadian mutants reveals mechanisms underlying regulation of sleep in Drosophila
    Mark N Wu
    Division of Sleep Medicine, Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Sleep 31:465-72. 2008
    ....
  24. pmc AKT and TOR signaling set the pace of the circadian pacemaker
    Xiangzhong Zheng
    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Curr Biol 20:1203-8. 2010
    ....
  25. pmc Dopamine acts through Cryptochrome to promote acute arousal in Drosophila
    Shailesh Kumar
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 26:1224-34. 2012
    ..We propose that CRY has a distinct role in acute responses to sensory stimuli: (1) circadian responses to light, as previously reported, and (2) noncircadian effects on arousal, as shown here...
  26. pmc Octopamine regulates sleep in drosophila through protein kinase A-dependent mechanisms
    Amanda Crocker
    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 28:9377-85. 2008
    ..However, this effect of PKA was not exerted in the mushroom bodies, a site previously associated with PKA action on sleep. These studies identify a novel pathway that regulates sleep in Drosophila...
  27. ncbi A sleep-promoting role for the Drosophila serotonin receptor 1A
    Quan Yuan
    Howard Hughes Medical Institute, Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Curr Biol 16:1051-62. 2006
    ..Serotonin is an important neurotransmitter known to affect many behaviors, but its role in sleep remains controversial...
  28. doi A critical period of sleep for development of courtship circuitry and behavior in Drosophila
    Matthew S Kayser
    Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 344:269-74. 2014
    ....
  29. pmc Interaction between sleep and metabolism in Drosophila with altered octopamine signaling
    Renske Erion
    Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 287:32406-14. 2012
    ....
  30. pmc A Drosophila model for age-associated changes in sleep:wake cycles
    Kyunghee Koh
    Howard Hughes Medical Institute, Department of Neuroscience, School of Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:13843-7. 2006
    ....
  31. ncbi Why a fly? Using Drosophila to understand the genetics of circadian rhythms and sleep
    Joan C Hendricks
    Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Sleep 27:334-42. 2004
    ..In conclusion, we sound some cautionary notes about some of the complexities of working with this "simple" organism...
  32. pmc Drosophila QVR/SSS modulates the activation and C-type inactivation kinetics of Shaker K(+) channels
    Terry Dean
    Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 31:11387-95. 2011
    ..Together, these results suggest that the role of SSS in the regulation of sleep in Drosophila correlates more strongly with the effects of SSS on Shaker kinetics than current magnitude...
  33. ncbi A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK
    J A Williams
    Howard Hughes Medical Institute, Center for Sleep and Respiratory Neurobiology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 293:2251-6. 2001
    ....
  34. ncbi Rest in Drosophila is a sleep-like state
    J C Hendricks
    Center for Sleep and Respiratory Neurobiology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA
    Neuron 25:129-38. 2000
    ..Finally, normal homeostatic regulation depends on the timeless but not the period central clock gene. Understanding the molecular features of Drosophila rest should shed new light on the mechanisms and function of sleep...
  35. pmc Identification of novel genes involved in light-dependent CRY degradation through a genome-wide RNAi screen
    Sriram Sathyanarayanan
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 22:1522-33. 2008
    ..This work identifies a novel regulatory network involved in light-dependent CRY degradation and demonstrates the power of a genome-wide RNAi approach for understanding circadian biology...
  36. pmc The effects of caffeine on sleep in Drosophila require PKA activity, but not the adenosine receptor
    Mark N Wu
    Division of Sleep Medicine, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 29:11029-37. 2009
    ..We suggest that chronic administration of caffeine promotes wakefulness in Drosophila, at least in part, by inhibiting cAMP phosphodiesterase activity...
  37. ncbi Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest
    Thomas C Dockendorff
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Neuron 34:973-84. 2002
    ..Morphological analysis of neurons required for normal circadian behavior reveals subtle abnormalities, suggesting that defects in axonal pathfinding or synapse formation may cause the observed behavioral defects...
  38. pmc Small-molecule screen in adult Drosophila identifies VMAT as a regulator of sleep
    Aleksandra H Nall
    Cell and Molecular Biology Program and Department of Neuroscience, Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 33:8534-40. 2013
    ..Overall, we identify VMAT as an important regulator of sleep in Drosophila and demonstrate that small-molecule screens provide an effective approach to identify genes and pathways that impact adult Drosophila behavior...
  39. pmc The circadian clock protein BMAL1 is necessary for fertility and proper testosterone production in mice
    J D Alvarez
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    J Biol Rhythms 23:26-36. 2008
    ..Other hormonal defects in male Bmal1 KO mice suggest that BMAL1 also has functions in reproductive physiology outside of the testis. These results enhance understanding of how the circadian clock regulates reproduction...
  40. pmc Quantitative genetic analysis of sleep in Drosophila melanogaster
    Susan T Harbison
    Howard Hughes Medical Institute, Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Genetics 178:2341-60. 2008
    ..The large mutational target that we observed implicates genes functioning in a variety of biological processes, suggesting that sleep may serve a number of different functions rather than a single purpose...
  41. ncbi Role of molecular oscillations in generating behavioral rhythms in Drosophila
    Z Yang
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Neuron 29:453-67. 2001
    ..Overexpression of either period or timeless, but especially timeless, attenuated behavioral rhythmicity and protein cycling in lateral neurons. We propose that the two proteins must cycle to drive rhythmic expression of downstream genes...
  42. ncbi Regulation of the cycling of timeless (tim) RNA
    G K Wang
    Department of Neuroscience and Center for Sleep and Respiratory Neurobiology, Howard Hughes Medical Institute, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    J Neurobiol 47:161-75. 2001
    ..Together, these data highlight molecular mechanisms that are critical for behavioral rhythms...
  43. pmc Energy stores are not altered by long-term partial sleep deprivation in Drosophila melanogaster
    Susan T Harbison
    Howard Hughes Medical Institute, Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    PLoS ONE 4:e6211. 2009
    ..These findings emphasize the importance of taking stress into account when evaluating the relationship between sleep loss and metabolism...
  44. pmc The circadian clock interacts with metabolic physiology to influence reproductive fitness
    Kanyan Xu
    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell Metab 13:639-54. 2011
    ..Flies maintained on this paradigm produce fewer eggs than those restricted to food at the normal time. These data suggest that desynchrony of endogenous rhythms, caused by aberrant feeding patterns, affects reproductive fitness...
  45. ncbi Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock
    P McNamara
    Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 105:877-89. 2001
    ..We propose that circadian or periodic availability of nuclear hormones may play a critical role in resetting a peripheral vascular clock...
  46. ncbi Rhythmic expression of timeless: a basis for promoting circadian cycles in period gene autoregulation
    A Sehgal
    Department of Neuroscience, University of Pennsylvania Medical Center, Philadelphia 19104, USA
    Science 270:808-10. 1995
    ....
  47. ncbi Positional cloning and sequence analysis of the Drosophila clock gene, timeless
    M P Myers
    Howard Hughes Medical Institute, National Science Foundation Science and Technology Center for Biological Timing, and Laboratory of Genetics, Rockefeller University, New York, NY 10021, USA
    Science 270:805-8. 1995
    ..Absence of sequence similarity to the PER dimerization motif (PAS) indicates that direct interaction between PER and TIM would require a heterotypic protein association...
  48. ncbi Regulation of the Drosophila protein timeless suggests a mechanism for resetting the circadian clock by light
    M Hunter-Ensor
    Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia 19104, USA
    Cell 84:677-85. 1996
    ..Since both PER and TIM RNA are unaffected by light treatment, the effects of light on TIM appear to be posttranscriptional...
  49. ncbi Altered entrainment and feedback loop function effected by a mutant period protein
    P Schotland
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 20:958-68. 2000
    ..These data have relevance for mechanisms of feedback repression, and they also address existing models for the differential behavioral response to light at different times of the night...
  50. ncbi Non-cyclic and developmental stage-specific expression of circadian clock proteins during murine spermatogenesis
    J D Alvarez
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Biol Reprod 69:81-91. 2003
    ..Noncircadian expression of clock genes was also found in the thymus, which, like the testis, is composed primarily of differentiating cells. We propose that cyclic expression of clock genes is suspended during cellular differentiation...
  51. ncbi Sleep in Drosophila is regulated by adult mushroom bodies
    William J Joiner
    Center for Sleep and Respiratory Neurobiology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    Nature 441:757-60. 2006
    ..Other manipulations of the mushroom bodies, such as electrical silencing, increasing excitation or ablation, also alter sleep. These results link sleep regulation to an anatomical locus known to be involved in learning and memory...
  52. pmc A conserved behavioral state barrier impedes transitions between anesthetic-induced unconsciousness and wakefulness: evidence for neural inertia
    Eliot B Friedman
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 5:e11903. 2010
    ....
  53. ncbi The thymus is similar to the testis in its pattern of circadian clock gene expression
    J D Alvarez
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Biol Rhythms 20:111-21. 2005
    ..The authors hypothesize that the circadian clock is not operational in immature, differentiating cells. Possibly, the clock starts in mature cells upon receipt of an initiating signal...
  54. pmc Probing the relative importance of molecular oscillations in the circadian clock
    Xiangzhong Zheng
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genetics 178:1147-55. 2008
    ..While the review is focused on Drosophila, we include some discussion of mammalian clocks to indicate the extent to which the questions concerning clock mechanisms are similar, regardless of the organism under study...
  55. ncbi A fly's eye view of circadian entrainment
    Lesley J Ashmore
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    J Biol Rhythms 18:206-16. 2003
    ..Temperature can also entrain the clock, although the mechanisms by which this occurs are also unclear...
  56. ncbi A role for the proteasome in the light response of the timeless clock protein
    N Naidoo
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 285:1737-41. 1999
    ..Degradation appeared to be preceded by tyrosine phosphorylation. Finally, TIM was ubiquitinated in response to light in cultured cells...
  57. pmc Conserved regions of the timeless (tim) clock gene in Drosophila analyzed through phylogenetic and functional studies
    A Ousley
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia 19104, USA
    Genetics 148:815-25. 1998
    ..Deletion of the segment mentioned above resulted in very long activity rhythms with periods ranging from 30.5 to 48 hr...
  58. pmc Identification of a circadian output circuit for rest:activity rhythms in Drosophila
    Daniel J Cavanaugh
    Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell 157:689-701. 2014
    ..Notably, selective activation or ablation of just six DH44+ PI cells causes arrhythmicity. These findings delineate a circuit through which clock cells can modulate locomotor rhythms...
  59. pmc Genetic analysis of sleep
    Amanda Crocker
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 24:1220-35. 2010
    ..Thus, while our understanding of sleep still remains rudimentary, rapid progress is expected from these recently initiated studies...
  60. ncbi A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis
    J C Hendricks
    Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 991 Maloney Building, 3600 Spruce St, Philadelphia, Pennsylvania, 19104 USA
    Nat Neurosci 4:1108-15. 2001
    ..In wild types, in vivo CREB activity increased after rest deprivation and remained elevated for a 72-hour recovery period. These data indicate that cAMP signaling has a non-circadian role in waking and rest homeostasis in Drosophila...
  61. ncbi Molecular components of the circadian system in Drosophila
    J A Williams
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    Annu Rev Physiol 63:729-55. 2001
    ..It has, however, become clear that in addition to the brain clock, autonomous or semi-autonomous clocks occur in peripheral tissues where they confer circadian regulation on specific functions...
  62. ncbi Alterations of per RNA in noncoding regions affect periodicity of circadian behavioral rhythms
    Y Chen
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    J Biol Rhythms 13:364-79. 1998
    ..These data indicate that the appropriate regulation of per RNA expression, effected by transcriptional as well as posttranscriptional mechanisms, is critical for the determination of circadian period...
  63. pmc Photic signaling by cryptochrome in the Drosophila circadian system
    F J Lin
    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 21:7287-94. 2001
    ..High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination...
  64. ncbi Molecular analysis of sleep: wake cycles in Drosophila
    A Sehgal
    Howard Hughes Medical Institute, USA
    Cold Spring Harb Symp Quant Biol 72:557-64. 2007
    ..Thus, the Drosophila model allows the use of cellular and molecular approaches that should ultimately lead to a better understanding of sleep biology...
  65. ncbi New routes for memory retrieval and reinforcement
    Terry Dean
    Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA
    Cell 139:225-7. 2009
    ..The different roles attributed to PPL1 neurons demonstrate heterogeneity of function in small neuronal subsets of the Drosophila brain...
  66. ncbi Response of the timeless protein to light correlates with behavioral entrainment and suggests a nonvisual pathway for circadian photoreception
    Z Yang
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia 19104, USA
    Neuron 21:215-23. 1998
    ..These results support the hypothesis that circadian entrainment does not rely on the visual system and likely involves a dedicated pathway for photoreception...
  67. ncbi Signaling components that drive circadian rhythms
    Garrick K Wang
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, 232 Stemmler Hall, 35th Street and Hamilton Walk, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Neurobiol 12:331-8. 2002
    ..Advances in circadian research over the past year include the common themes of redundancy and plasticity...
  68. pmc Speed control: cogs and gears that drive the circadian clock
    Xiangzhong Zheng
    Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
    Trends Neurosci 35:574-85. 2012
    ..In this review, we examine the regulatory mechanisms that contribute to setting the pace of the circadian oscillator...
  69. ncbi REV-ving up the clock
    J D Alvarez
    Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA
    Dev Cell 3:150-2. 2002
    ..Circadian rhythms are generated by a transcription/translation feedback loop consisting of two limbs, one positive and one negative. The nuclear orphan receptor, REV-ERBalpha, is identified as a molecular link coupling these two limbs...
  70. ncbi Molecular regulation of circadian rhythms in Drosophila and mammals
    E L Meyer-Bernstein
    Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania Medical School, Philadelphia, 19104-6101, USA
    Neuroscientist 7:496-505. 2001
    ..Although expression of several mammalian clock gene products is also altered in response to light, the photoreceptor(s) involved have not yet been defined...
  71. ncbi An abrupt shift in the day/night cycle causes desynchrony in the mammalian circadian center
    Mamoru Nagano
    Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osakasayama City, Osaka 589 8511, Japan
    J Neurosci 23:6141-51. 2003
    ..This dissociation and slow resynchronization of endogenous oscillators within the SCN after an LD cycle shift suggests a mechanism for the physiological symptoms that constitute jet lag...
  72. ncbi Circadian rhythms: finer clock control
    J D Alvarez
    Nature 419:798-9. 2002
  73. pmc A Drosophila model for Angelman syndrome
    Yaning Wu
    Section of Molecular Cell and Developmental Biology, Institute for Cell and Molecular Biology, University of Texas, 1 University Station A4800, Austin, TX 78712, USA
    Proc Natl Acad Sci U S A 105:12399-404. 2008
    ..We conclude that dube3a mutants are a valid model for Angelman syndrome, with great potential for identifying the elusive UBE3A substrates relevant to the disease...
  74. pmc Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish
    Julie A Williams
    Center for Advanced Biotechnology and Medicine and Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Piscataway 08854 5603, USA
    Sleep 30:389-400. 2007
    ..The Drosophila model for sleep provides a powerful system to identify and test the role of sleep-relevant molecules...
  75. ncbi Restoration of circadian behavioural rhythms in a period null Drosophila mutant (per01) by mammalian period homologues mPer1 and mPer2
    Yasufumi Shigeyoshi
    Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Chuo Ku, Kobe 650 0017, Japan
    Genes Cells 7:163-71. 2002
    ..In this study, we investigated the functional conservation of per by introducing the mouse mPer1 and mPer2 genes, driven by the Drosophila timeless (tim) promoter, into Drosophila melanogaster...
  76. ncbi Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome
    Sean M J McBride
    Section of Molecular Cardiology, Department of Medicine, Medical Scientist Training Program, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Neuron 45:753-64. 2005
    ..They also raise the possibility that compounds having similar effects on metabotropic glutamate receptors may ameliorate cognitive and behavioral defects observed in Fragile X patients...

Research Grants4

  1. Cycling of Circadian Rhythm Proteins
    Amita Sehgal; Fiscal Year: 2009
    ..3) Generate and characterize additional mutants of wdb and tws. (4) Determine how the clock controls the cycling of tws and address the relevance of this cycling for behavioral rhythms. ..
  2. Cycling of Circadium Rhythm Proteins
    Amita Sehgal; Fiscal Year: 2006
    ..3) Generate and characterize additional mutants of wdb and tws. (4) Determine how the clock controls the cycling of tws and address the relevance of this cycling for behavioral rhythms. ..
  3. Cycling of Circadian Rhythm Proteins
    Amita Sehgal; Fiscal Year: 2007
    ..3) Generate and characterize additional mutants of wdb and tws. (4) Determine how the clock controls the cycling of tws and address the relevance of this cycling for behavioral rhythms. ..