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dc.contributor.advisorPatrick Emery, Ph.D.
dc.contributor.authorMurad, Alejandro D.
dc.date2022-08-11T08:08:41.000
dc.date.accessioned2022-08-23T16:04:22Z
dc.date.available2022-08-23T16:04:22Z
dc.date.issued2007-10-25
dc.date.submitted2008-05-05
dc.identifier.doi10.13028/04tt-g435
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31676
dc.description.abstractMost organisms, from cyanobacteria to humans are equipped with circadian clocks. These endogenous and self-sustained pacemakers allow organisms to adapt their physiology and behavior to daily environmental variations, and to anticipate them. The circadian clock is synchronized by environmental cues (i.e. light and temperature fluctuations). The fruit fly, Drosophila melanogaster, is well established as a model for the study of circadian rhythms. Molecular mechanisms of the Drosophilacircadian clock are conserved in mammals. Using genetic screens, several essential clock proteins (PER, TIM, CLK, CYC, DBT, SGG and CK-II) were identified in flies. Homologs of most of these proteins are also involved in generating mammalian circadian rhythms. In addition, there are only six neuronal groups in the adult fly brain (comprising about 75 pairs of cells) that express high levels of clock genes. The simplicity of this system is ideal for the study of the neural circuitry underlying behavior. The first half of this dissertation focuses on a genetic screen designed to identify novel genes involved in the circadian light input pathway. The screen was based on previous observations that a mutation in the circadian photoreceptor CRYPTOCHROME (CRY) allows flies to remain rhythmic in constant light (LL), while wild type flies are usually arrhythmic under this condition. 2000 genes were overexpressed and those that showed a rhythmic behavior in LL (like crymutants) were isolated. The candidate genes isolated in the screen present a wide variety of biological functions. These include genes involved in protein degradation, signaling pathways, regulation of transcription, and even a pacemaker gene. In this dissertation, I describe work done in order to validate and characterize such candidates. The second part of this dissertation focuses on identifying the pacemaker neurons that drive circadian rhythms in constant light (LL) when the pacemaker gene period is overexpressed. We found that a subset of pacemaker neurons, the DN1s, is responsible for driving rhythms in constant light. This attractive finding reveals a novel role for the DN1s in driving behavioral rhythms under constant conditions and suggests a mechanism for seasonal adaptation in Drosophila.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectCircadian Rhythm
dc.subjectNeurons
dc.subjectDrosophila
dc.subjectBiological Clocks
dc.subjectInvertebrate Photoreceptors
dc.subjectDrosophila Proteins
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectAnimal Experimentation and Research
dc.subjectCells
dc.subjectGenetic Phenomena
dc.subjectNervous System
dc.titleMolecular and Neuronal Analysis of Circadian Photoresponses in <em>Drosophila</em>: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1357&amp;context=gsbs_diss&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/357
dc.legacy.embargo2007-10-25T00:00:00-07:00
dc.identifier.contextkey504097
refterms.dateFOA2022-08-27T04:45:51Z
html.description.abstract<p>Most organisms, from cyanobacteria to humans are equipped with circadian clocks. These endogenous and self-sustained pacemakers allow organisms to adapt their physiology and behavior to daily environmental variations, and to anticipate them. The circadian clock is synchronized by environmental cues (i.e. light and temperature fluctuations).</p> <p>The fruit fly, <em>Drosophila melanogaster</em>, is well established as a model for the study of circadian rhythms. Molecular mechanisms of the <em>Drosophila</em>circadian clock are conserved in mammals. Using genetic screens, several essential clock proteins (PER, TIM, CLK, CYC, DBT, SGG and CK-II) were identified in flies. Homologs of most of these proteins are also involved in generating mammalian circadian rhythms. In addition, there are only six neuronal groups in the adult fly brain (comprising about 75 pairs of cells) that express high levels of clock genes. The simplicity of this system is ideal for the study of the neural circuitry underlying behavior.</p> <p>The first half of this dissertation focuses on a genetic screen designed to identify novel genes involved in the circadian light input pathway. The screen was based on previous observations that a mutation in the circadian photoreceptor CRYPTOCHROME (CRY) allows flies to remain rhythmic in constant light (LL), while wild type flies are usually arrhythmic under this condition. 2000 genes were overexpressed and those that showed a rhythmic behavior in LL (like <em>cry</em>mutants) were isolated. The candidate genes isolated in the screen present a wide variety of biological functions. These include genes involved in protein degradation, signaling pathways, regulation of transcription, and even a pacemaker gene. In this dissertation, I describe work done in order to validate and characterize such candidates.</p> <p>The second part of this dissertation focuses on identifying the pacemaker neurons that drive circadian rhythms in constant light (LL) when the pacemaker gene <em>period</em> is overexpressed. We found that a subset of pacemaker neurons, the DN1s, is responsible for driving rhythms in constant light. This attractive finding reveals a novel role for the DN1s in driving behavioral rhythms under constant conditions and suggests a mechanism for seasonal adaptation in <em>Drosophila</em>.</p>
dc.identifier.submissionpathgsbs_diss/357
dc.contributor.departmentEmery Lab
dc.contributor.departmentNeurobiology
dc.description.thesisprogramNeuroscience


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