Location of Repository

Genetic and bioinformatic screening for behavioural mutations in Drosophila melanogaster

By Edward Wilhelm Green


In the post-genomic era, the question of how genes give rise to the observable diversity of morphology, physiology, behaviour and disease susceptibility is becoming of one central importance. Even in a model system as well studied as the fruit fly Drosophila melanogaster, the function of the vast majority of genes, and the mechanisms by which they give rise to such diversity, remains unknown. \ud Drosophila behaviour represents a sensitive system in which to evaluate novel methods of determining gene function. Traditionally the analysis of behavioural phenotypes has represented a time consuming, highly subjective process. I have developed a suite of automated analysis tools (the BeFly! package) that has not only made such analyses both quicker and more objective, but has also allowed data to be examined in greater depth by making complex algorithms more accessible to users. \ud The BeFly! package was initially used to characterise a serendipitously identified circadian mutant strain provisionally named Party on. As the Party on gene could not be conclusively mapped, and a meta analysis of existing circadian microarray data suggested that many circadian genes remained to be identified, BeFly!’s high throughput tools were employed in a novel systems biology screen in which phenotypic analysis was combined with gene expression data to identify likely gene function. \ud This approach generated a number of novel candidate clock genes, the roles of which were further analysed using RNAi knockdown, confirming that the neuropeptide gene Adipokinetic hormone-like played a role in the clock mechanism. Given the success of our new strategy, it was widened to identify genes controlling sleep in Drosophila, leading to the identification of several genes associated with distinct aspects of sleep. \ud In conclusion, the tools and methods developed in this thesis represent a novel, sensitive method for determining gene function applicable beyond the Drosophila model

Publisher: University of Leicester
Year: 2010
OAI identifier: oai:lra.le.ac.uk:2381/8656

Suggested articles



  1. (2007). 5-HT2 receptors in Drosophila are expressed in the brain and modulate aspects of circadian behaviors.
  2. (2007). A blend of two circadian clocks, seasoned to perfection.
  3. (2003). A clockwork web: circadian timing in brain and periphery, in health and disease.
  4. (2000). A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression.
  5. (2004). A constitutively active cryptochrome in Drosophila melanogaster.
  6. (2006). A Drosophila model for age-associated changes in sleep:wake cycles.
  7. (1986). A Drosophila mutation that eliminates a calciumdependent potassium current.
  8. (2006). A dynamic role for the mushroom bodies in promoting sleep in Drosophila.
  9. (1976). A functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: A clock for all seasons.
  10. (2007). A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes Dev.
  11. (2005). A G proteincoupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior.
  12. (2008). A genetic screen for sleep and circadian mutants reveals mechanisms underlying regulation of sleep in Drosophila.
  13. (2007). A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila.
  14. (2007). A global analysis of genetic interactions in Caenorhabditis elegans.
  15. (1997). A kinder, gentler genetic analysis of behavior: dissection gives way to modulation.
  16. (1996). A light-entrainment mechanism for the Drosophila circadian clock.
  17. (2007). A mathematical model of the Drosophila circadian clock with emphasis on posttranslational mechanisms.
  18. (2007). A molecular basis for natural selection at the timeless locus in Drosophila melanogaster.
  19. (1998). A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless.
  20. (1993). A new biological rhythm mutant of Drosophila melanogaster that identifies a gene with an essential embryonic function.
  21. (1997). A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate expression with
  22. (2001). A new role for cryptochrome in a Drosophila circadian oscillator.
  23. (2001). A noncircadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis.
  24. (2008). A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size. Genes Dev.
  25. (1999). A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila.
  26. (2008). A plastic clock: how circadian rhythms respond to environmental cues in Drosophila.
  27. (1998). A practical guide to wavelet analysis.
  28. (1994). A promoterless period gene mediates behavioral rhythmicity and cyclical per expression in a restricted subset of the Drosophila nervous system.
  29. (2005). A resetting signal between Drosophila pacemakers synchronizes morning and evening activity.
  30. (2002). A role for casein kinase 2alpha in the Drosophila circadian clock.
  31. (2003). A role for CK2 in the Drosophila circadian oscillator.
  32. (2007). A role for the molecular chaperone protein
  33. (2009). A role for the PERIOD:PERIOD homodimer in the Drosophila circadian clock.
  34. (1999). A role for the proteasome in the light response of the timeless clock protein.
  35. (2001). A role for the segment polarity gene shaggy/GSK-3 in the Drosophila circadian clock.
  36. (2003). A self-sustaining, light-entrainable circadian oscillator in the Drosophila brain.
  37. (2006). A sleep-promoting role for the Drosophila serotonin receptor 1A.
  38. (2007). A subset of dorsal neurons modulates circadian behavior and light responses in Drosophila.
  39. (2002). A temperature-dependent timing mechanism is involved in the circadian system that drives locomotor rhythms in the fruit fly Drosophila melanogaster. Zoolog Sci.
  40. (2008). A video method to study Drosophila sleep.
  41. (2007). Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila.
  42. (2001). Adipokinetic hormones of insect: release, signal transduction, and responses.
  43. (2004). An integrative genomics approach to the reconstruction of gene networks in segregating populations. Cytogenet.Genome Res.
  44. (2009). An isoformspecific mutant reveals a role of PDP1 epsilon in the circadian oscillator.
  45. (2006). Analysis of locomotor activity rhythms in Drosophila.
  46. (2004). and Heidelberg Fly Array Consortium.
  47. (2005). and Members of the Toxicogenomics Research Consortium.
  48. (1984). Animal sleep: a review of sleep duration across phylogeny.
  49. (1974). Aperture synthesis with a non-regular distribution of interferometer baselines.
  50. (2001). Applications of the DFT/CLEAN technique to solar time series.
  51. (2001). Are complex behaviors specified by dedicated regulatory genes? Reasoning from Drosophila.
  52. (2006). Attention-like processes underlying optomotor performance in a Drosophila choice maze.
  53. (1993). Behavior in light-dark cycles of Drosophila mutants that are arrhythmic, blind, or both.
  54. (2006). BioGRID: a general repository for interaction datasets. Nucleic Acids Res.
  55. (1965). Biological clocks, the functions, ancient and modern, of biological oscillations.
  56. (1994). Block in nuclear localization of period protein by a second clock mutation, timeless.
  57. (2005). Canlization, Crptic Variation, and Developmental Buffering: A Critical Examination and Analytical Perspective.
  58. (1985). Characterization of a pigment-dispersing hormone in eyestalks of the fiddler crab Uca pugilator.
  59. (1991). Characterization of Andante, a new Drosophila clock mutant, and its interactions with other clock mutants.
  60. Chromosome cohesion is regulated by a clock gene paralogue TIM-1.
  61. (1987). Circadian and ultradian rhythms in period mutants of Drosophila melanogaster.
  62. (2002). Circadian clock and microarrays: mammalian genome gets rhythm. Trends Genet.
  63. (1965). Circadian Clocks.
  64. (2003). Circadian control of eclosion: interaction between a central and peripheral clock in Drosophila melanogaster.
  65. (2008). Circadian entrainment to red light
  66. (2006). Circadian orchestration of the hepatic proteome.
  67. (2001). Circadian photoreception in Drosophila: functions of cryptochrome in peripheral and central clocks.
  68. (2008). Circadian regulation of a limited set of conserved microRNAs in Drosophila.
  69. (2001). Circadian regulation of gene expression systems in the Drosophila head.
  70. (2009). Circadian regulation of olfactory receptor neurons in the cockroach antenna.
  71. (2006). Circadian regulator CLOCK is a histone acetyltransferase.
  72. (1996). Circadian rhythm generation, expression and entrainment in a molluscan model system. Prog.Brain Res.
  73. (1989). Circadian rhythm mutations in Drosophila melanogaster affect short-term fluctuations in the male's courtship song.
  74. (2005). Circadian rhythms from multiple oscillators: lessons from diverse organisms.
  75. (2008). Circadian- and lightdependent regulation of resting membrane potential and spontaneous action potential firing of Drosophila circadian pacemaker neurons.
  76. (2008). Clines in clock genes: fine-tuning circadian rhythms to the environment. Trends Genet.
  77. (2004). Clock gene evolution and functional divergence.
  78. (1990). Clock mutations alter developmental timing in Drosophila.
  79. (2007). Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component. Genes Dev.
  80. (1998). Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim.
  81. (1956). Concept of general and specific combining ability in relation to diallel crossing systems.
  82. (1994). Constant light suppresses sleep and circadian rhythms in pigeons without consequent sleep rebound in darkness.
  83. (2006). Control of daily transcript oscillations in Drosophila by light and the circadian clock. PLoS Genet.
  84. (2000). Correlates of sleep and waking in Drosophila melanogaster.
  85. (2004). Coupled oscillators control morning and evening locomotor behaviour of Drosophila.
  86. (2008). Cryptochrome mediates lightdependent magnetosensitivity in Drosophila.
  87. (2003). Cryptochrome, compound eyes, Hofbauer-Buchner eyelets, and ocelli play different roles in the entrainment and masking pathway of the locomotor activity rhythm in the fruit fly Drosophila melanogaster.
  88. (2006). Cyanobacterial circadian pacemaker: Kai protein complex dynamics in the KaiC phosphorylation cycle in vitro.
  89. (1998). CYCLE is a second bHLHPAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless.
  90. (1999). Cycling vrille expression is required for a functional Drosophila clock.
  91. (2008). D1 receptor activation in the mushroom bodies rescues sleep-loss-induced learning impairments in Drosophila.
  92. (2007). Daytime sleep condenses the time course of motor memory consolidation.
  93. (2000). dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex.
  94. (2001). Defining the role of Drosophila lateral neurons in the control of circadian rhythms in motor activity and eclosion by targeted genetic ablation and PERIOD protein overexpression.
  95. (2007). Development and morphology of the clock-gene-expressing lateral neurons of Drosophila melanogaster.
  96. (2000). Differential control of morning and evening components in the activity rhythm of Drosophila melanogaster--sex-specific differences suggest a different quality of activity.
  97. (2000). Differential regulation of circadian pacemaker output by separate clock genes in Drosophila.
  98. (1996). Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectives.
  99. (2005). Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease.
  100. (2005). Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic period mutant of Drosophila.
  101. (2010). Dissecting differential gene expression within the circadian neuronal circuit of Drosophila.
  102. (2003). Distinction between color photoreceptor cell fates is controlled by Prospero in Drosophila.
  103. (2003). DNA microarray analyses of circadian timing: the genomic basis of biological time.
  104. (2002). Dopa decarboxylase(Ddc)-GAL4 dramatically reduces life span.
  105. (2005). Dopamine is a regulator of arousal in the fruit fly.
  106. (2005). Dopaminergic modulation of arousal in Drosophila.
  107. (1998). double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation.
  108. (2009). DOUBLETIME plays a non-catalytic role to mediate CLOCK phosphorylation and repress CLOCK-dependent transcription within the Drosophila circadian clock.
  109. (2002). Drosophila as a new model organism for the neurobiology of aggression?
  110. (2008). Drosophila ATF-2 regulates sleep and locomotor activity in pacemaker neurons.
  111. (2003). Drosophila clock can generate ectopic circadian clocks.
  112. (2006). Drosophila CLOCK is constitutively expressed in circadian oscillator and non-oscillator cells.
  113. (2002). Drosophila CLOCK protein is under posttranscriptional control and influences light-induced activity.
  114. (2004). Drosophila cryb mutation reveals two circadian clocks that drive locomotor rhythm and have different responsiveness to light. J.Insect Physiol.
  115. (2006). Drosophila CRYPTOCHROME is a circadian transcriptional repressor.
  116. (2007). Drosophila ebony activity is required in glia for the circadian regulation of locomotor activity.
  117. (1991). Drosophila ebony mutants have altered circadian activity rhythms but normal eclosion rhythms.
  118. (2005). Drosophila GPCR Han is a receptor for the circadian clock neuropeptide PDF.
  119. (2007). Drosophila Hyperkinetic mutants have reduced sleep and impaired memory.
  120. (1997). Drosophila melanogaster deficient in protein kinase A manifests behavior-specific arrhythmia but normal clock function.
  121. (1998). Drosophila photoreceptors contain an autonomous circadian oscillator that can function without period mRNA cycling.
  122. (2001). Drosophila: genetics meets behaviour.
  123. (2005). Drosophilia: A Laboratory Handbook.
  124. (2000). Ectopic G-protein expression in dopamine and serotonin neurons blocks cocaine sensitization in Drosophila melanogaster.
  125. (2003). Effects of combining a cryptochrome mutation with other visual-system variants on entrainment of locomotor and adult-emergence rhythms in Drosophila.
  126. (2006). Electrical hyperexcitation of lateral ventral pacemaker neurons desynchronizes downstream circadian oscillators in the fly circadian circuit and induces multiple behavioral periods.
  127. (2002). Electrical silencing of Drosophila pacemaker neurons stops the free-running circadian clock.
  128. (2008). Electrical silencing of PDF neurons advances the phase of non-PDF clock neurons in Drosophila.
  129. (2002). Electrophysiological correlates of rest and activity in Drosophila melanogaster.
  130. (2005). Emerging technologies for gene manipulation in Drosophila melanogaster.
  131. (1996). Engineering the Drosophila genome: chromosome rearrangements by design.
  132. (1998). Epistatic interactions between smell-impaired loci in Drosophila melanogaster.
  133. (2005). Essentials of sleep recordings in Drosophila: moving beyond sleep time. Methods Enzymol.
  134. (1998). Evidence that the TIM light response is relevant to light-induced phase shifts in Drosophila melanogaster.
  135. (1985). Evolution of an instinct under long-term divergent selection for geotaxis in domesticated populations of Drosophila melanogaster.
  136. (2007). Evolution of genes and genomes on the Drosophila phylogeny.
  137. (1992). Expression of the period clock gene within different cell types in the brain of Drosophila adults and mosaic analysis of these cells' influence on circadian behavioral rhythms.
  138. (2005). Flexibility in a gene network affecting a simple behavior in Drosophila melanogaster.
  139. (1997). Fly Pushing: The Theory and Practice of Drosophila Genetics.
  140. (2005). FlyTracker: Real-Time Analysis Of Insect Courtship.
  141. (2006). Functional analysis of circadian pacemaker neurons in Drosophila melanogaster.
  142. (1987). Further evidence that the circadian clock in Drosophila is a population of coupled ultradian oscillators.
  143. (2003). GAL4 causes developmental defects and apoptosis when expressed in the developing eye of Drosophila melanogaster.
  144. (2002). GAL4 system in Drosophila: a fly geneticist's Swiss army knife.
  145. (2007). Genetic screening for signal transduction in the era of network biology.
  146. (2002). Genome-wide expression analysis in Drosophila reveals genes controlling circadian behavior.
  147. (2004). Genome-wide high-throughput screens in functional genomics.
  148. (2002). Genome-wide transcriptional orchestration of circadian rhythms in Drosophila.
  149. (2007). Glutamate and its metabotropic receptor in Drosophila clock neuron circuits.
  150. (2006). Gravitaxis in Drosophila melanogaster: a forward genetic screen.
  151. (2007). Harnessing naturally randomized transcription to infer regulatory relationships among genes. Genome Biol.
  152. (2000). Hebb and homeostasis in neuronal plasticity.
  153. (2004). Hemolymph sugar homeostasis and starvation-induced hyperactivity affected by genetic manipulations of the adipokinetic hormone-encoding gene in Drosophila melanogaster.
  154. (1989). High-resolution analysis of locomotor activity rhythms in disconnected, a visual-system mutant of Drosophila melanogaster.
  155. (2006). Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation.
  156. (2004). Homeostatic regulation of sleep in arrhythmic Siberian hamsters.
  157. (1999). How a circadian clock adapts to seasonal decreases in temperature and day length.
  158. (2009). HSP90, a capacitor of behavioral variation.
  159. (2002). Huygens’s clocks.
  160. (1995). Identification and expression of the Drosophila adipokinetic hormone gene.
  161. (2006). Identification of a biomarker for sleep drive in flies and humans.
  162. (2002). Identification of genes involved in Drosophila melanogaster geotaxis, a complex behavioral trait.
  163. Identification of novel genes involved in light-dependent CRY degradation through a genomewide RNAi screen. Genes Dev.
  164. (2008). Identification of SLEEPLESS, a sleep-promoting factor.
  165. (2009). Identifying genes involved in cyclic processes by combining gene expression analysis and prior knowledge.
  166. (2002). Identifying some determinants of "jet lag" and its symptoms: a study of athletes and other travellers. Br.J.Sports Med.
  167. (2007). Induction of Drosophila behavioral and molecular circadian rhythms by temperature steps in constant light.
  168. (2002). Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster.
  169. (2007). Integration of light and temperature in the regulation of circadian gene expression in Drosophila.
  170. (1999). Interlocked feedback loops within the Drosophila circadian oscillator.
  171. (1995). Introduction to Quantitative Genetics.
  172. (2008). Is sleep essential? PLoS Biol.
  173. (1998). Isolation and chronobiological analysis of a neuropeptide pigment-dispersing factor gene in Drosophila melanogaster.
  174. (2006). JETLAG resets the Drosophila circadian clock by promoting light-induced degradation of TIMELESS.
  175. Large ventral lateral neurons modulate arousal and sleep in Drosophila.
  176. (1913). Le Probleme Physiologique Du Sommeil.
  177. (2008). Lethargus is a Caenorhabditis elegans sleep-like state.
  178. (2008). Light-arousal and circadian photoreception circuits intersect at the large
  179. (2009). Light-Dependent Interactions between the Drosophila Circadian Clock Factors Cryptochrome, Jetlag, and Timeless.
  180. (1974). Mammalian sleep, longevity, and energy metabolism.
  181. (2006). Mapping of serotonin, dopamine, and histamine in relation to different clock neurons in the brain of Drosophila.
  182. (2005). Membrane electrical excitability is necessary for the free-running larval Drosophila circadian clock.
  183. (1997). Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance.
  184. (2007). Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes. PLoS Comput.Biol.
  185. (2001). Microarray analysis and organization of circadian gene expression in Drosophila.
  186. (2008). Mid-range Ultradian Rhythms in Drosophila and the Circadian Clock Problem.
  187. (2004). Migratory sleeplessness in the white-crowned sparrow (Zonotrichia leucophrys gambelii). PLoS Biol.
  188. (2004). Mistaken identifiers: gene name errors can be introduced inadvertently when using Excel in bioinformatics.
  189. (2008). Modulation of GABAA receptor desensitization uncouples sleep onset and maintenance in Drosophila.
  190. (2008). Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep.
  191. (2007). Monitoring and analyzing Drosophila circadian locomotor activity. Methods Mol.Biol.
  192. (2007). Moonlight shifts the endogenous clock of Drosophila melanogaster.
  193. (2004). Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain.
  194. (2004). Multi-oscillatory control of eclosion and oviposition rhythms in Drosophila melanogaster: evidence from limits of entrainment studies.
  195. (2006). Multiple mechanisms limit the duration of wakefulness in Drosophila brain.
  196. (1999). Mushroom body ablation impairs short-term memory and long-term memory of courtship conditioning in Drosophila melanogaster.
  197. (2005). Mutations in and deletions of the Ca2+ channel-encoding gene cacophony, which affect courtship song in Drosophila, have novel effects on heartbeating.
  198. (1991). Mutual interactions between optic lobe circadian pacemakers in the cricket Gryllus bimaculatus.
  199. (2007). Natural selection favors a newly derived timeless allele in Drosophila melanogaster.
  200. (1997). Natural variation in a Drosophila clock gene and temperature compensation.
  201. (2004). Network biology: understanding the cell's functional organization.
  202. (2007). Network neighborhood analysis with the multi-node topological overlap measure.
  203. (2006). Neural circuits underlying circadian behavior in Drosophila melanogaster.
  204. (2000). Neuroanatomy of cells expressing clock genes in Drosophila: transgenic manipulation of the period and timeless genes to mark the perikarya of circadian pacemaker neurons and their projections.
  205. (2004). Neuroendocrine control of larval ecdysis behavior in Drosophila: complex regulation by partially redundant neuropeptides.
  206. (2007). Neurohormonal and neuromodulatory control of sleep in Drosophila. Cold Spring Harb.Symp.Quant.Biol.
  207. (2004). Novel features of cryptochrome-mediated photoreception in the brain circadian clock of Drosophila.
  208. (2006). Of flies and man: Drosophila as a model for human complex traits. Annu.Rev.Genomics Hum.Genet.
  209. (2008). Organization of the Drosophila circadian control circuit.
  210. (2003). Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J.Sleep Res.
  211. (2008). PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit.
  212. (2006). PDF cycling in the dorsal protocerebrum of the Drosophila brain is not necessary for circadian clock function.
  213. (2005). PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors.
  214. (1997). PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes.
  215. (2007). PDP1epsilon functions downstream of the circadian oscillator to mediate behavioral rhythms.
  216. (2002). Peptidomics of the larval Drosophila melanogaster central nervous system.
  217. (1999). PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription.
  218. (1995). PER protein interactions and temperature compensation of a circadian clock in Drosophila.
  219. (2006). PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription. Genes Dev.
  220. (2006). PER-TIM interactions in living Drosophila cells: an interval timer for the circadian clock.
  221. (2008). Peripheral circadian clock for the cuticle deposition rhythm
  222. (2007). Pharmacological imposition of sleep slows cognitive decline and reverses dysregulation of circadian gene expression in a transgenic mouse model of Huntington's disease.
  223. (1983). Physiological correlates of prolonged sleep deprivation in rats.
  224. (1997). Pigment-dispersing hormone shifts the phase of the circadian pacemaker of the cockroach Leucophaea maderae.
  225. (1994). Pleiotropy of behavioural genes.
  226. (1971). Populations of biochemical oscillators as circadian clocks.
  227. (1995). Positional cloning and sequence analysis of the Drosophila clock gene, timeless.
  228. (2004). Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A.
  229. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
  230. (2005). Prevalence, associated risks, and treatment patterns of insomnia.
  231. (2009). pySolo: a complete suite for sleep analysis in Drosophila.
  232. (2008). Quantitative genetic analysis of sleep in Drosophila melanogaster.
  233. (1989). Reciprocal behaviour associated with altered homeostasis and photosensitivity of Drosophila clock mutants.
  234. (2005). Reduced sleep in Drosophila Shaker mutants.
  235. (1953). Regularly occurring periods of eye motility, and concomitant phenomena, during sleep.
  236. (1996). Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye.
  237. (2002). Resetting the circadian clock by social experience in Drosophila melanogaster.
  238. (1998). Resonating circadian clocks enhance fitness in cyanobacteria.
  239. (2000). Rest in Drosophila is a sleep-like state.
  240. (1995). Restoration of brain energy metabolism as the function of sleep.
  241. (2008). Reverse engineering the genotype-phenotype map with natural genetic variation.
  242. (2007). Rhythm defects caused by newly engineered null mutations in Drosophila's cryptochrome gene.
  243. (2006). Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions.
  244. (2008). Rhythmic E-box binding by CLK-CYC controls daily cycles in per and tim transcription and chromatin modifications.
  245. (2004). Robustness of cellular functions.
  246. (2002). Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime.
  247. (2001). Role of molecular oscillations in generating behavioral rhythms in Drosophila.
  248. (2005). Role of the neuropeptide CCAP in Drosophila cardiac function.
  249. (1986). Role of the optic lobes in the regulation of the locomotor activity rhythm of Drosophila melanogaster: behavioral analysis of neural mutants.
  250. (2003). Seasonality and circadian phase delay: prospective evidence that winter lowering of mood is associated with a shift towards Eveningness.
  251. (1981). Selection for central excitatory state (CES) in the blow fly Phormia regina.
  252. (2002). Sequential nuclear accumulation of the clock proteins period and timeless in the pacemaker neurons of Drosophila melanogaster.
  253. (2008). Setting clock speed in mammals: the CK1 epsilon tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins.
  254. (1961). Sign of taxis as a property of the genotype.
  255. (2002). Signal analysis of behavioral and molecular cycles.
  256. (2007). Simpler mode of inheritance of transcriptional variation
  257. (2008). SIRT1 is a circadian deacetylase for core clock components.
  258. (2005). Sleep and wakefulness modulate gene expression in Drosophila.
  259. (1995). Sleep as neuronal detoxification and restitution. Behav.Brain Res.
  260. (2005). Sleep deprivation induces the unfolded protein response in mouse cerebral cortex.
  261. (2006). Sleep function and synaptic homeostasis. Sleep Med.Rev.
  262. (2006). Sleep in Drosophila is regulated by adult mushroom bodies.
  263. (1994). Sleep in insects and nonmammalian vertebrates.
  264. (2008). Sleep medicine in occupational health.
  265. (2008). Sleep: hitting the reset button.
  266. (1997). Spatial and temporal expression of the period and timeless genes in the developing nervous system of Drosophila: newly identified pacemaker candidates and novel features of clock gene product cycling.
  267. (2000). Specific genetic interference with behavioral rhythms in Drosophila by expression of inverted repeats.
  268. (2000). Specific sequences outside the E-box are required for proper per expression and behavioral rescue.
  269. (2007). Statistical analysis of biological rhythm data. Methods Mol.Biol.
  270. (2002). Stress response genes protect against lethal effects of sleep deprivation in Drosophila.
  271. (1972). Studies on the scutellar bristles of Drosophila melanogaster. II. Long-term selection for high bristle number in the Oregon RC strain and correlated responses in abdominal chaetae.
  272. (1974). Suppressing drosophila circadian rhythm with dim light.
  273. (2005). System-level identification of transcriptional circuits underlying mammalian circadian clocks.
  274. (2004). Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome.
  275. (2009). Systems genetics of complex traits in Drosophila melanogaster.
  276. (2000). takeout, a novel Drosophila gene under circadian clock transcriptional regulation.
  277. (2003). Targeted ablation of CCAP neuropeptide-containing neurons of Drosophila causes specific defects in execution and circadian timing of ecdysis behavior.
  278. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
  279. (1968). Temperature compensation of the circadian oscillation in drosophila pseudoobscura and its entrainment by temperature cycles. J.Insect Physiol.
  280. Temperature cycles drive Drosophila circadian oscillation in constant light that otherwise induces behavioural arrhythmicity.
  281. (2009). Temperature entrainment of Drosophila's circadian clock involves the gene nocte and signaling from peripheral sensory tissues to the brain.
  282. (2005). Temperature synchronization of the Drosophila circadian clock.
  283. (2004). The adaptive value of circadian clocks: an experimental assessment in cyanobacteria.
  284. (2003). The art of entrainment.
  285. (2004). The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes.
  286. (2001). The circadian clock of fruit flies is blind after elimination of all known photoreceptors.
  287. (2009). The COP9 signalosome is required for light-dependent timeless degradation and Drosophila clock resetting.
  288. (1918). The correlations between relatives on the supposesition of Mendelian inheritance.
  289. (1998). The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila.
  290. (2004). The doubletime and CKII kinases collaborate to potentiate Drosophila PER transcriptional repressor activity.
  291. (2007). The Drosophila circadian network is a seasonal timer.
  292. (1998). The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon.
  293. (1998). The Drosophila CLOCK protein undergoes daily rhythms in abundance, phosphorylation, and interactions with the PER-TIM complex.
  294. (1992). The Drosophila couch potato protein is expressed in nuclei of peripheral neuronal precursors and shows homology to RNA-binding proteins. Genes Dev.
  295. (2008). The Drosophila FMRP and LARK RNA-binding proteins function together to regulate eye development and circadian behavior.
  296. (2000). The Drosophila takeout gene is a novel molecular link between circadian rhythms and feeding behavior.
  297. (1995). The effects of period mutations and light on the activity rhythms of Drosophila melanogaster.
  298. (2002). The Fbox protein slimb controls the levels of clock proteins period and timeless.
  299. (2001). The flexible genome.
  300. (1994). The free radical flux theory of sleep.
  301. (2008). The genetic architecture of complex behaviors: lessons from Drosophila.
  302. (2002). The genetic architecture of Drosophila sensory bristle number.
  303. (2009). The genetics of quantitative traits: challenges and prospects.
  304. (2000). The genome sequence of Drosophila melanogaster.
  305. (2007). The human circadian clock's seasonal adjustment is disrupted by daylight saving time.
  306. (2007). The human disease network.
  307. (2009). The implications of multiple circadian clock origins.
  308. (2005). The ion channel narrow abdomen is critical for neural output of the Drosophila circadian pacemaker.
  309. (2004). The neuropeptide pigment-dispersing factor coordinates pacemaker interactions in the Drosophila circadian system.
  310. (2009). The nocturnal activity of fruit flies exposed to artificial moonlight is partly caused by direct light effects on the activity level that bypass the endogenous clock.
  311. (2001). The nonA gene in Drosophila conveys species-specific behavioral characteristics.
  312. (1911). The Origin of Five Mutations
  313. (1995). The period clock gene is expressed in central nervous system neurons which also produce a neuropeptide that reveals the projections of circadian pacemaker cells within the brain of Drosophila melanogaster.
  314. (2000). The period E-box is sufficient to drive circadian oscillation of transcription in vivo.
  315. (2001). The role of Drosophila mushroom body signaling in olfactory memory.
  316. (2008). The role of microRNAs (miRNA) in circadian rhythmicity.
  317. (1997). The Science of Timekeeping Hewlett Packard Application Note 1289.
  318. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene.
  319. (1998). The timSL mutant affects a restricted portion of the Drosophila melanogaster circadian cycle.
  320. (2002). The ups and downs of daily life: profiling circadian gene expression in Drosophila.
  321. (1997). The vrille gene of Drosophila is a maternal enhancer of decapentaplegic and encodes a new member of the bZIP family of transcription factors.
  322. (1995). Time of symptom onset of eight common medical emergencies.
  323. (1987). Time series with CLEAN. Deviation of a spectrum.
  324. (1999). timrit Lengthens circadian period in a temperature-dependent manner through suppression of PERIOD protein cycling and nuclear localization.
  325. (2005). Total sleep deprivation.
  326. (2007). Transgenesis upgrades for Drosophila melanogaster.
  327. (2005). Transgenic cAMP response element reporter flies for monitoring circadian rhythms. Methods Enzymol.
  328. (2005). Underestimating the societal costs of impaired alertness: safety, health and productivity risks.
  329. (2002). Unifying the genetics of behavior.
  330. (2009). Use-dependent plasticity in clock neurons regulates sleep need in Drosophila.
  331. (2007). Using FlyAtlas to identify better Drosophila melanogaster models of human disease.
  332. (2008). Using genetic markers to orient the edges in quantitative trait networks: the NEO software.
  333. (2006). Veela defines a molecular link between Cryptochrome and Timeless in the light-input pathway to Drosophila's circadian clock.
  334. (2001). Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning.
  335. (2003). VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator.
  336. (2003). vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock.
  337. (2006). Waking experience affects sleep need in Drosophila.
  338. (2008). WAVECLOCK: wavelet analysis of circadian oscillation.
  339. (2007). Wellcome Trust Case Control Consortium.
  340. (2007). What is there left to learn about the Drosophila clock? Cold Spring Harb.Symp.Quant.Biol.
  341. (2009). Widespread changes in synaptic markers as a function of sleep and wakefulness in Drosophila.
  342. (2008). Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.