# overview
Research in the Bell-Pedersen lab focuses on determining how the circadian clock functions in organisms to regulate daily rhythms in gene expression, behavior, and physiology. The molecular clock in higher eukaryotes involves a master clock in the brain regulating clocks in peripheral tissues, posing significant obstacles for understanding circadian output mechanisms. Thus, a major strength of our work is using a single-celled model eukaryote, Neurospora crassa, to elucidate the underlying mechanisms of rhythmic gene expression and protein synthesis. Clock dysfunction in humans is associated with a wide range of diseases, including cardiovascular disease, cancer, metabolic disorders, mental illness, sleep disorders, and aging. In addition, daily changes in metabolism and cell division rates influence the efficacy and toxicity of many pharmaceuticals, including cancer drugs. Therefore, knowing how clocks work to control rhythmic gene expression, and what they regulate, is critical for the development of therapeutics. Research to understand clock-controlled rhythmic gene expression has focused primarily on transcriptional mechanisms, and little was known about posttranscriptional control. We discovered that the clock regulates highly conserved translation initiation and elongation factors, tRNA synthetase levels, and ribosome heterogeneity. This regulation determines what mRNAs are rhythmically translated and the accuracy of the translation process (translation fidelity). We are capitalizing on these exciting discoveries to determine how the clock regulates translation fidelity. These studies will provide the foundation for understanding the impact of daily rhythms in translation fidelity on protein diversity beyond what is encoded for in the genome.

# keywords[]
Reverse Transcriptase Polymerase Chain Reaction

# keywords[]
1.1 Normal Biological Development And Functioning

# keywords[]
3102 Bioinformatics And Computational Biology

# keywords[]
1.1 Normal Biological Development And Functioning

# educationAndTraining[].organization.label
State University of New York - (Albany, New York, United States)

# educationAndTraining[].organization.label
State University of New York - (Albany, New York, United States)

# educationAndTraining[].organization.label
Dartmouth College - (Hanover, New Hampshire, United States)

# publications[].label
Complexity of the Neurospora crassa Circadian Clock System: Multiple Loops and Oscillators

# publications[].label
Circadian Gene Selection for Time-to-event Phenotype by Integrating CNV and RNAseq Data.

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Circadian and light-induced expression of luciferase in Neurospora crassa.

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Circadian clock control of tRNA synthetases in Neurospora crassa

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A novel cryptochrome-dependent oscillator in Neurospora crassa.

# publications[].label
INTRON MOBILITY IN PHAGE-T4 IS DEPENDENT UPON A DISTINCTIVE CLASS OF ENDONUCLEASES AND INDEPENDENT OF DNA-SEQUENCES ENCODING THE INTRON CORE - MECHANISTIC AND EVOLUTIONARY IMPLICATIONS

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The Neurospora crassa pheromone precursor genes are regulated by the mating type locus and the circadian clock.

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The Neurospora circadian clock: simple or complex?

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Circadian rhythmicity mediated by temporal regulation of the activity of p38 MAPK.

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

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The Neurospora Transcription Factor ADV-1 Transduces Light Signals and Temporal Information to Control Rhythmic Expression of Genes Involved in Cell Fusion.

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Molecular Genetics of Circadian Rhythms in Neurospora Crassa

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Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae.

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I-TEVI, THE ENDONUCLEASE ENCODED BY THE MOBILE TD INTRON, RECOGNIZES BINDING AND CLEAVAGE DOMAINS ON ITS DNA TARGET

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

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A circadian clock translational control mechanism targets specific mRNAs to cytoplasmic messenger ribonucleoprotein granules.

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Effects of altered Clock gene expression on the pacemaker properties of SCN2.2 cells and oscillatory properties of NIH/3T3 cells.

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The genetic and molecular dissection of a prototypic circadian system.

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Circadian clock control of eIF2 phosphorylation is necessary for rhythmic translation initiation.

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

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GENES WITHIN GENES - INDEPENDENT EXPRESSION OF PHAGE-T4 INTRON OPEN READING FRAMES AND THE GENES IN WHICH THEY RESIDE

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Multiple oscillators regulate circadian gene expression in Neurospora.

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

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A ras-1bd Mauriceville strain for mapping mutations in Oak Ridge ras-1bdstrains

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The genetics of circadian rhythms in Neurospora.

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The Third International Symposium on Fungal Stress - ISFUS.

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Genome-wide characterization of light-regulated genes in Neurospora crassa.

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A site-specific endonuclease and co-conversion of flanking exons associated with the mobile td intron of phage T4**Presented at the Albany Conference on RNA: Catalysis, Splicing, Evolution. Rensselaerville, N.Y. (U.S.A.), 22-25 September, 1988.

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Distinct signaling pathways from the circadian clock participate in regulation of rhythmic conidiospore development in Neurospora crassa.

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Genetic interactions between clock mutations in Neurospora crassa: can they help us to understand complexity?

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Guidelines for Genome-Scale Analysis of Biological Rhythms.

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The cell free protein synthesis system from the model filamentous fungus Neurospora crassa.

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Transcription factors in light and circadian clock signaling networks revealed by genomewide mapping of direct targets for neurospora white collar complex.

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Genes within genes: independent expression of phage T4 intron open reading frames and the genes in which they reside.

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Circadian clock-controlled genes isolated from Neurospora crassa are late night- to early morning-specific.

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

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vvd is required for light adaptation of conidiation-specific genes of Neurospora crassa, but not circadian conidiation.

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Correction to: inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

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Circadian activation of the mitogen-activated protein kinase MAK-1 facilitates rhythms in clock-controlled genes in Neurospora crassa.

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Circadian Clock-Controlled Translation of Specific Neurospora crassamRNAs Requires Rhythmic eIF2 Activity and P-Bodies

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Two circadian timing circuits in Neurospora crassa cells share components and regulate distinct rhythmic processes.

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Circadian rhythms from multiple oscillators: lessons from diverse organisms.

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INTRON MOBILITY IN THE T-EVEN PHAGES - HIGH-FREQUENCY INHERITANCE OF GROUP-I INTRONS PROMOTED BY INTRON OPEN READING FRAMES

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Distinct cis-acting elements mediate clock, light, and developmental regulation of the Neurospora crassa eas (ccg-2) gene.

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Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential.

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

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A circadian oscillator in Aspergillus spp. regulates daily development and gene expression.

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Direct transcriptional control of a p38 MAPK pathway by the circadian clock in Neurospora crassa.

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Diverse roles for MAPK signaling in circadian clocks.

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Biological Rhythms and Photoperiodism in Plants                     . P. J. Lumsden , A. J. Millar

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Neurospora clock-controlled gene 9 (ccg-9) encodes trehalose synthase: circadian regulation of stress responses and development.

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THE INCONSISTENT DISTRIBUTION OF INTRONS IN THE T-EVEN PHAGES INDICATES RECENT GENETIC EXCHANGES

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Analysis of expressed sequence tags from two starvation, time-of-day-specific libraries of Neurospora crassa reveals novel clock-controlled genes.

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Complexity of the Neurospora crassa circadian clock system: multiple loops and oscillators.

# publications[].label
Defining a mechanism of circadian output in Neurospora crassa: temporal regulation of a MAP kinase pathway

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Transcriptional profiling of the chick pineal gland, a photoreceptive circadian oscillator and pacemaker.

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Regulation of gene expression in Neurospora crassa with a copper responsive promoter.

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Circadian rhythms in Neurospora crassa and other filamentous fungi.

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Keeping pace with Neurospora circadian rhythms.

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Assignment of an essential role for the Neurospora frequency gene in circadian entrainment to temperature cycles.

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

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A SITE-SPECIFIC ENDONUCLEASE AND CO-CONVERSION OF FLANKING EXONS ASSOCIATED WITH THE MOBILE TD-INTRON OF PHAGE-T4

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Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism.

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Circadian Clock Control of Translation Initiation Factor eIF2 Activity Requires eIF2-Dependent Recruitment of Rhythmic PPP-1 Phosphatase in Neurospora crassa.

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Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2.

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

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3 Molecular Genetics of Circadian Rhythms in Neurospora Crassa

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Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity.

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The genome sequence of the filamentous fungus Neurospora crassa.

# publications[].label
Inhibition of p38 MAPK activity leads to cell type-specific effects on the molecular circadian clock and time-dependent reduction of glioma cell invasiveness.

# publications[].label
THE NEUROSPORA CIRCADIAN CLOCK-CONTROLLED GENE, CCG-2, IS ALLELIC TO EAS AND ENCODES A FUNGAL HYDROPHOBIN REQUIRED FOR FORMATION OF THE CONIDIAL RODLET LAYER

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Overexpression of White Collar-1 (WC-1) activates circadian clock-associated genes, but is not sufficient to induce most light-regulated gene expression in Neurospora crassa.

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The Neurospora circadian clock regulates a transcription factor that controls rhythmic expression of the output eas(ccg-2) gene.

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A connection between MAPK pathways and circadian clocks.

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Isoform-specific regulation of rhythmic gene expression by alternative polyadenylation

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The genetic basis of the circadian clock: identification of frq and FRQ as clock components in Neurospora.

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The Neurospora circadian clock-controlled gene, ccg-2, is allelic to eas and encodes, a fungal hydrophobin required for formation of the conidial rodlet layer

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The rhythms of life: circadian output pathways in Neurospora.

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A TRANSCRIPTION TERMINATOR IN THE THYMIDYLATE SYNTHASE (THYA) STRUCTURAL GENE OF ESCHERICHIA-COLI AND CONSTRUCTION OF A VIABLE THYA-KMR DELETION

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Understanding circadian rhythmicity in Neurospora crassa: from behavior to genes and back again.

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Transcriptional response to glucose starvation and functional analysis of a glucose transporter of Neurospora crassa.

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Circadian clock control of tRNA synthetases in Neurospora crassa

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A genetic selection for circadian output pathway mutations in Neurospora crassa.

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Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism in Neurospora crassa.

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

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Structure of the translating Neurospora ribosome arrested by cycloheximide.

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

# publications[].label
The 2009 George W. Beadle Award Jay C. Dunlap Honors and Awards

# publications[].label
The Neurospora crassa OS MAPK pathway-activated transcription factor ASL-1 contributes to circadian rhythms in pathway responsive clock-controlled genes.

# researcherOn[].label
Molecular Genetic Analysis of Fungal Circadian Rhythms

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

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

# researcherOn[].label
Mechanisms of Circadian Clock Control of mRNA Translation

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

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

# researcherOn[].label
Determining the Mechanism of Temperature Compensation of the Circadian Clock

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

# researcherOn[].label
Biannual Meeting of the Society for Research on Biological Rhythms

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

# researcherOn[].label
Systems Biology of the Circadian Clock Output Network

# 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

# etdChairOf[].label
Huang, He (2009-05). The light mutant oscillator (LMO); a novel circadian oscillator in Neurospora crassa. Master's Thesis.

# etdChairOf[].label
Lewis, Zachary Austin (2005-02). Control of rhythmic output from the circadian clock in Neurospora crassa. Doctoral Dissertation.

# etdChairOf[].label
Petty, Amanda Lee (2018-05). Understanding Circadian Clock Regulation of Ribosome Heterogeneity in Neurospora crassa. Master's Thesis.

# etdChairOf[].label
Vitalini, Michael William (2009-05). Uncovering the circadian output pathways of Neurospora crassa. Doctoral Dissertation.

# etdChairOf[].label
Nsa, Imade Yolanda (2013-08). A Novel Cryptochrome-Dependent Oscillator in Neurospora crassa. Doctoral Dissertation.

# etdChairOf[].label
Goldsmith, Charles Sidney (2013-08). Regulation of the p38 MAPK Signaling Pathway by the Circadian Clock. Doctoral Dissertation.

# etdChairOf[].label
Greene, Andrew Vanderford (2006-10). Organization of the circadian clock and control of rhythmicity in fungi. Doctoral Dissertation.

# etdChairOf[].label
Jayant Kumar Ojha, Nikita (2016-05). Characterizing the Role of a Phosphorelay in the Circadian Regulation of the OS Mapk Pathway in Neurospora crassa. Master's Thesis.

# etdChairOf[].label
Caster, Stephen Z (2016-08). The Stress Response and Circadian Regulation of Translation in Neurospora crassa. Doctoral Dissertation.

# etdChairOf[].label
Ibarra, Oneida (2017-12). Understanding the Circadian Output Gene Network Using the Clock-Controlled Transcription Factor ADV-1 in Neurospora Crassa. Master's Thesis.

# etdChairOf[].label
Karki, Shanta (2019-10). Circadian Clock Regulation of Translation Initiation in Neurospora crassa Through Phosphorylation of a Highly Conserved Initiation Factor eIF2a. Doctoral Dissertation.

# etdChairOf[].label
Bennett, Lindsay Danielle (2013-12). Mapping Circadian Output Pathways in Neurospora crassa. Doctoral Dissertation.

# etdChairOf[].label
Dekhang, Rigzin N (2015-05). Understanding Circadian Output Networks in Neurospora Crassa. Doctoral Dissertation.