# overview
A diverse array of organisms including prokaryotic and eukaryotic microbes, plants, and animals display daily rhythms in physiology, metabolism and/or behavior. These rhythms are not passively driven by environmental cycles of light and temperature, but are actively controlled by endogenous circadian clocks that are set by environmental cycles, keep time in the absence of environmental cues, and activate overt physiological, metabolic and behavioral rhythms at the appropriate time of day. This remarkable conservation of circadian clock function through evolution suggests that maintaining synchrony with the environment is of fundamental importance. Our understanding of the circadian clock is particularly important for human health and well-being. The clearest examples of circadian clock dysfunction are those that result in abnormal sleep-wake cycles, but clock disturbances are also associated with other ailments including epilepsy, cerebrovascular disease, depression, and seasonal affective disorder. The realization that disorders of the sleep-wake cycle such as Familial Advanced Sleep Phase Syndrome can result from alterations in clock gene function underscores the clinical importance of understanding the molecular organization of the circadian system.

Work in my laboratory focuses on defining the molecular mechanisms that drive circadian clock function in the fruit fly, Drosophila melanogaster. We previously found that the core timekeeping mechanism is based on core and interlocked transcriptional feedback loops. Our studies currently focus on (1) defining post-translational regulatory mechanisms that operate in the core loop to set the 24 hour period, (2) determining whether interlocked loops are important for circadian timekeeping and/or output, (3) understanding how circadian oscillator cells are determined during development, and (4) defining mechanisms that control rhythms in olfactory and gustatory physiology and behavior.

# keywords[]
GTP-Binding Protein Alpha Subunits, Gi-Go

# keywords[]
Intracellular Signaling Peptides And Proteins

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# keywords[]
Nuclear Receptor Subfamily 1, Group D, Member 1

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# educationAndTraining[].organization.label
Indiana University Bloomington - (Bloomington, Indiana, United States)

# educationAndTraining[].organization.label
Howard Hughes Medical Institute - (Chevy Chase, Maryland, United States)

# educationAndTraining[].organization.label
Southern Methodist University - (Dallas, Texas, United States)

# awardsAndHonors[].label
John W. Lyons Jr. '59 Endowed Chair in Biology

# publications[].label
The blue-light photoreceptor CRYPTOCHROME is expressed in a subset of circadian oscillator neurons in the Drosophila CNS.

# publications[].label
Go contributes to olfactory reception in Drosophila melanogaster.

# publications[].label
Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition.

# publications[].publisher
American Association for Cancer Research (AACR)

# publications[].label
Interlocked feedback loops within the Drosophila circadian oscillator.

# publications[].publisher
American Association for the Advancement of Science (AAAS)

# publications[].label
A promoterless period gene mediates behavioral rhythmicity and cyclical per expression in a restricted subset of the Drosophila nervous system.

# publications[].label
Transcription regulation within the circadian clock: the E-box and beyond.

# publications[].label
A DOUBLETIME kinase binding domain on the Drosophila PERIOD protein is essential for its hyperphosphorylation, transcriptional repression, and circadian clock function.

# publications[].label
The 69 bp circadian regulatory sequence (CRS) mediates per-like developmental, spatial, and circadian expression and behavioral rescue in Drosophila.

# publications[].label
Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels.

# publications[].label
TRITHORAX-dependent arginine methylation of HSP68 mediates circadian repression by PERIOD in the monarch butterfly.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A.

# publications[].label
An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock.

# publications[].label
A role for the adult fat body in Drosophila male courtship behavior.

# publications[].label
Rhythmic E-box binding by CLK-CYC controls daily cycles in per and tim transcription and chromatin modifications.

# publications[].label
Specific sequences outside the E-box are required for proper per expression and behavioral rescue.

# publications[].label
Spatial and circadian regulation of cry in Drosophila.

# publications[].label
Structure of the Spec1 gene encoding a major calcium-binding protein in the embryonic ectoderm of the sea urchin, Strongylocentrotus purpuratus.

# publications[].label
VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator.

# publications[].label
Disruption of synaptic transmission or clock-gene-product oscillations in circadian pacemaker cells of Drosophila cause abnormal behavioral rhythms.

# publications[].label
The circadian timekeeping system of Drosophila.

# publications[].label
A unified nomenclature system for the Drosophila odorant receptors. Drosophila Odorant Receptor Nomenclature Committee.

# publications[].label
Transcriptional feedback loop regulation, function, and ontogeny in Drosophila.

# publications[].label
PDP1epsilon functions downstream of the circadian oscillator to mediate behavioral rhythms.

# publications[].label
VRILLE Controls PDF Neuropeptide Accumulation and Arborization Rhythms in Small Ventrolateral Neurons to Drive Rhythmic Behavior in Drosophila.

# publications[].label
Circadian transcription: passing the HAT to CLOCK.

# publications[].label
Phosphorylation of the transcription activator CLOCK regulates progression through a  24-h feedback loop to influence the circadian period in Drosophila.

# publications[].label
CLOCK stabilizes CYCLE to initiate clock function in Drosophila.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
G protein-coupled receptor kinase 2 is required for rhythmic olfactory responses in Drosophila.

# publications[].label
A Drosophila nonvisual arrestin is required for the maintenance of olfactory sensitivity.

# publications[].label
Circadian clocks in antennal neurons are necessary and sufficient for olfaction rhythms in Drosophila.

# publications[].label
Circadian oscillations in period gene mRNA levels are transcriptionally regulated.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex.

# publications[].label
Simulation of Drosophila circadian oscillations, mutations, and light responses by a model with VRI, PDP-1, and CLK.

# publications[].label
Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression.

# publications[].label
Survey of transcripts in the adult Drosophila brain.

# publications[].label
Drosophila CRY Entrains Clocks in Body Tissues to Light and Maintains Passive Membrane Properties in a Non-clock Body Tissue Independent of Light.

# publications[].label
Molecular genetic analysis of circadian timekeeping in Drosophila.

# publications[].label
An RNAi screen of protein kinase genes identifies novel components of the circadian oscillator in Drosophila

# publications[].label
DOUBLETIME plays a noncatalytic role to mediate CLOCK phosphorylation and repress CLOCK-dependent transcription within the Drosophila circadian clock.

# publications[].label
Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Drosophila photoreceptors contain an autonomous circadian oscillator that can function without period mRNA cycling.

# publications[].label
Circadian rhythms in olfactory responses of Drosophila melanogaster.

# publications[].label
The multiple roles of per in the Drosophila circadian clock

# publications[].label
Rapid attenuation of circadian clock gene oscillations in the rat heart following ischemia-reperfusion.

# publications[].label
vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock.

# publications[].label
From biological clock to biological rhythms.

# publications[].label
Circadian oscillators of Drosophila and mammals.

# publications[].label
The circadian clock within the cardiomyocyte is essential for responsiveness of the heart to fatty acids.

# publications[].label
Circadian clocks: the tissue is the issue.

# publications[].label
DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila.

# publications[].label
Circadian Activators Are Expressed Days before They Initiate Clock Function in Late Pacemaker Neurons from Drosophila.

# publications[].label
Circadian timekeeping and output mechanisms in animals.

# publications[].label
Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock.

# publications[].label
Constitutive overexpression of the Drosophila period protein inhibits period mRNA cycling.

# publications[].label
Drosophila CLOCK protein is under posttranscriptional control and influences light-induced activity.

# publications[].label
The intrinsic circadian clock within the cardiomyocyte.

# publications[].label
Unusual sequence conservation in the 5' and 3' untranslated regions of the sea urchin spec mRNAs.

# publications[].label
Central and peripheral circadian oscillators in Drosophila.

# publications[].label
Circadian rhythm of temperature preference and its neural control in Drosophila.

# publications[].label
Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogaster.

# publications[].label
Time to taste: circadian clock function in the Drosophila gustatory system.

# publications[].label
Reflections on contributing to "big discoveries" about the fly clock: Our fortunate paths as post-docs with 2017 Nobel laureates Jeff Hall, Michael Rosbash, and Mike Young.

# publications[].label
per mRNA cycling is locked to lights-off under photoperiodic conditions that support circadian feedback loop function.

# publications[].label
Regulation of gustatory physiology and appetitive behavior by the Drosophila circadian clock.

# publications[].label
The period E-box is sufficient to drive circadian oscillation of transcription in vivo.

# publications[].label
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.

# publications[].label
How a circadian clock adapts to seasonal decreases in temperature and day length.

# publications[].label
Transcriptional Feedback Loop Regulation, Function, and Ontogeny in Drosophila

# publications[].label
Activating inhibitors and inhibiting activators: a day in the life of a fly.

# publications[].label
Spec2 genes of Strongylocentrotus purpuratus. Structure and differential expression in embryonic aboral ectoderm cells.

# publications[].label
Effects of TWIN-OF-EYELESS on Clock Gene Expression and Central-Pacemaker Neuron Development in Drosophila.

# publications[].label
Use of firefly luciferase activity assays to monitor circadian molecular rhythms in vivo and in vitro.

# publications[].label
Spike amplitude of single-unit responses in antennal sensillae is controlled by the Drosophila circadian clock.

# publications[].label
NEMO kinase contributes to core period determination by slowing the pace of the Drosophila circadian oscillator.

# publications[].label
Essential and expendable features of the circadian timekeeping mechanism.

# publications[].label
The circadian output gene takeout is regulated by Pdp1epsilon.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Molecular mechanisms of circadian timekeeping in Drosophila

# publications[].label
A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock.

# publications[].label
Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment.

# publications[].label
Novel proteins belonging to the troponin C superfamily are encoded by a set of mRNAs in sea urchin embryos.

# publications[].label
Circadian disruption of memory consolidation in Drosophila.

# publications[].label
Two alternatively spliced transcripts from the Drosophila period gene rescue rhythms having different molecular and behavioral characteristics.

# publications[].label
Measuring circadian rhythms in olfaction using electroantennograms

# publications[].label
Perspectives: neurobiology. The CRYs fo flies and mice.

# publications[].publisher
American Association for the Advancement of Science (AAAS)

# publications[].label
Crosstalk between vrille transcripts, proteins, and regulatory elements controlling circadian rhythms and development in Drosophila.

# publications[].label
Circadian oscillations in protein and mRNA levels of the period gene of Drosophila melanogaster.

# publications[].label
CLOCK expression and regulation during development in Drosophila

# publications[].label
A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila melanogaster.

# publications[].label
CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the putative Drosophila ortholog of CLOCK INTERACTING PROTEIN CIRCADIAN.

# publications[].label
CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE.

# publications[].label
CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos.

# publications[].label
A post-transcriptional mechanism contributes to circadian cycling of a per-beta-galactosidase fusion protein.

# publications[].publisher
Proceedings of the National Academy of Sciences

# publications[].label
Central and peripheral circadian oscillator mechanisms in flies and mammals.

# publications[].label
PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription.

# publications[].label
Use of consensus oligonucleotides for detecting and isolating nucleic acids encoding calcium binding domains of the troponin C superfamily.

# publications[].label
A new role for cryptochrome in a Drosophila circadian oscillator.

# publications[].label
Light and temperature control the contribution of specific DN1 neurons to Drosophila circadian behavior.

# publications[].label
Circadian rhythms from multiple oscillators: lessons from diverse organisms.

# publications[].label
The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for Development of Circadian Pacemaker Neuron Processes That Support Rhythmic Activity in Constant Darkness But Not during Light/Dark Cycles.

# publications[].label
Analysis of period mRNA cycling in Drosophila head and body tissues indicates that body oscillators behave differently from head oscillators.

# publications[].label
Drosophila CLOCK is constitutively expressed in circadian oscillator and non-oscillator cells.

# researcherOn[].label
Circadian clock activation and tissue specificity in Drosophila

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of Neurological Disorders and Stroke

# researcherOn[].label
NIh-Developing Cell Lines From Clock Neurons In Drosophila

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.label
National Institutes of Health - (Bethesda, Maryland, United States)

# researcherOn[].awardedBy.preferredLabel
DHHS-NIH-National Institute of General Medical Science

# streetAddress
Texas A&M University; Biology; 3258 TAMU

# inTheNews[].label
2020 AAAS Fellows approved by the AAAS Council

# inTheNews[].label
AAAS announces leading scientists elected as 2020 fellows

# etdChairOf[].label
Agrawal, Parul (2016-08). Characterizing Novel Circadian Clock Functions for Drosophila Phosphatases and Non-clock Functions for Circadian Photoreceptors. Doctoral Dissertation.

# etdChairOf[].label
Caster, Courtney Marie (2017-08). Investigating the Evolution of the Molecular Clock Mechanism Using the Housefly, Musca domestica. Master's Thesis.

# etdChairOf[].label
Chatterjee, Abhishek (2011-05). Connecting the Circadian Clock with Chemosensation. Doctoral Dissertation.

# etdChairOf[].label
Krishnan, Parthasarathy (2008-05). Cellular and molecular mechanisms that regulate olfactory rhythms in drosophila melanogaster. Doctoral Dissertation.

# etdChairOf[].label
Liu, Tianxin (2017-08). Circadian Clock Development and Initiation in Drosophila melanogaster. Doctoral Dissertation.

# etdChairOf[].label
Zhou, Jian (2017-08). Characterizing the Function of Clockwork Orange in the Circadian Feedback Loops in Drosophila melanogaster. Doctoral Dissertation.

# etdChairOf[].label
Gunawardhana, Kushan Lakshitha (2018-05). Characterization of Vrille Function in the Drosophila Circadian Clock. Doctoral Dissertation.