Rhythmic Behavior Is Controlled by the Srm160 Splicing Factor In
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CURRICULUM VITAE Joseph S. Takahashi Howard Hughes Medical
CURRICULUM VITAE Joseph S. Takahashi Howard Hughes Medical Institute Department of Neuroscience University of Texas Southwestern Medical Center 5323 Harry Hines Blvd., NA4.118 Dallas, Texas 75390-9111 (214) 648-1876, FAX (214) 648-1801 Email: [email protected] DATE OF BIRTH: December 16, 1951 NATIONALITY: U.S. Citizen by birth EDUCATION: 1981-1983 Pharmacology Research Associate Training Program, National Institute of General Medical Sciences, Laboratory of Clinical Sciences and Laboratory of Cell Biology, National Institutes of Health, Bethesda, MD 1979-1981 Ph.D., Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, Oregon, Dr. Michael Menaker, Advisor. Summer 1977 Hopkins Marine Station, Stanford University, Pacific Grove, California 1975-1979 Department of Zoology, University of Texas, Austin, Texas 1970-1974 B.A. in Biology, Swarthmore College, Swarthmore, Pennsylvania PROFESSIONAL EXPERIENCE: 2013-present Principal Investigator, Satellite, International Institute for Integrative Sleep Medicine, World Premier International Research Center Initiative, University of Tsukuba, Japan 2009-present Professor and Chair, Department of Neuroscience, UT Southwestern Medical Center 2009-present Loyd B. Sands Distinguished Chair in Neuroscience, UT Southwestern 2009-present Investigator, Howard Hughes Medical Institute, UT Southwestern 2009-present Professor Emeritus of Neurobiology and Physiology, and Walter and Mary Elizabeth Glass Professor Emeritus in the Life Sciences, Northwestern University -
About the Fly Clock: Our Fortunate Paths As Post-Docs with 2017 Nobel Laureates Jeff Hall, Michael Rosbash, and Mike Young
Swarthmore College Works Biology Faculty Works Biology 6-1-2018 Reflections On Contributing oT “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young Kathleen King Siwicki Swarthmore College, [email protected] P. E. Hardin J. L. Price Follow this and additional works at: https://works.swarthmore.edu/fac-biology Part of the Biology Commons, and the Neuroscience and Neurobiology Commons Let us know how access to these works benefits ouy Recommended Citation Kathleen King Siwicki, P. E. Hardin, and J. L. Price. (2018). "Reflections On Contributing oT “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young". Neurobiology Of Sleep And Circadian Rhythms. Volume 5, 58-67. DOI: 10.1016/j.nbscr.2018.02.004 https://works.swarthmore.edu/fac-biology/559 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License. This work is brought to you for free by Swarthmore College Libraries' Works. It has been accepted for inclusion in Biology Faculty Works by an authorized administrator of Works. For more information, please contact [email protected]. Neurobiology of Sleep and Circadian Rhythms 5 (2018) 58–67 Contents lists available at ScienceDirect Neurobiology of Sleep and Circadian Rhythms journal homepage: www.elsevier.com/locate/nbscr 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 ⁎ Kathleen K. Siwickia, Paul E. -
Regulation of Drosophila Rest: Activity Rhythms by a Microrna and Aging
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2012 Regulation of Drosophila Rest: Activity Rhythms by a Microrna and Aging Wenyu Luo University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Family, Life Course, and Society Commons, Genetics Commons, and the Neuroscience and Neurobiology Commons Recommended Citation Luo, Wenyu, "Regulation of Drosophila Rest: Activity Rhythms by a Microrna and Aging" (2012). Publicly Accessible Penn Dissertations. 540. https://repository.upenn.edu/edissertations/540 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/540 For more information, please contact [email protected]. Regulation of Drosophila Rest: Activity Rhythms by a Microrna and Aging Abstract Although there has been much progress in deciphering the molecular basis of the circadian clock, major questions remain about clock mechanisms and about the control of behavior and physiology by the clock. In particular, mechanisms that transmit time-of-day signals from the clock and produce rhythmic behaviors are poorly understood. Also, it is not known why rest:activity rhythms break down with age. In this thesis, we used a Drosophila model to address some of these questions. We identified a pathway that is required downstream of the clock for rhythmic rest:activity and also explored the mechanisms that account for deterioration of behavioral rhythms with age. By investigating candidate circadian mutants identified in a previous genetic screen in the laboratory, we discovered a circadian function of a microRNA gene, miR-279. We found that miR-279 acts through the JAK/STAT pathway to drive rest:activity rhythms. -
G1/S Cell Cycle Regulators Mediate Effects of Circadian Dysregulation on Tumor Growth and Provide Targets for Timed Anticancer Treatment
RESEARCH ARTICLE G1/S cell cycle regulators mediate effects of circadian dysregulation on tumor growth and provide targets for timed anticancer treatment 1 2 1 1 3 Yool Lee , Nicholas F. LahensID , Shirley ZhangID , Joseph Bedont , Jeffrey M. Field , 1 Amita SehgalID * 1 Penn Chronobiology, Howard Hughes Medical Institute, Department of Neuroscience, Perelman School of a1111111111 Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2 Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, a1111111111 Philadelphia, Pennsylvania, United States of America, 3 Department of Systems Pharmacology and a1111111111 Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, a1111111111 Pennsylvania, United States of America a1111111111 * [email protected] Abstract OPEN ACCESS Citation: Lee Y, Lahens NF, Zhang S, Bedont J, Circadian disruption has multiple pathological consequences, but the underlying mecha- Field JM, Sehgal A (2019) G1/S cell cycle nisms are largely unknown. To address such mechanisms, we subjected transformed cul- regulators mediate effects of circadian tured cells to chronic circadian desynchrony (CCD), mimicking a chronic jet-lag scheme, dysregulation on tumor growth and provide targets and assayed a range of cellular functions. The results indicated a specific circadian clock± for timed anticancer treatment. PLoS Biol 17(4): e3000228. https://doi.org/10.1371/journal. dependent increase in cell proliferation. Transcriptome analysis revealed up-regulation of pbio.3000228 G1/S phase transition genes (myelocytomatosis oncogene cellular homolog [Myc], cyclin Academic Editor: Achim Kramer, Charite - D1/3, chromatin licensing and DNA replication factor 1 [Cdt1]), concomitant with increased UniversitaÈtsmedizin Berlin, GERMANY phosphorylation of the retinoblastoma (RB) protein by cyclin-dependent kinase (CDK) 4/6 Received: September 20, 2018 and increased G1-S progression. -
Oncogenic Myc Disrupts the Molecular Clock and Metabolism in Cancer
ONCOGENIC MYC DISRUPTS THE MOLECULAR CLOCK AND METABOLISM IN CANCER CELLS AND DROSOPHILA by Annie Lee Hsieh A dissertation submitted to Johns Hopkins University in conformity with the requirement for the degree of Doctor of Philosophy Baltimore, Maryland March 2016 ©Annie Lee Hsieh 2016 All right reserved Abstract Circadian rhythm is a biological rhythm with a period about 24 hours, which coordinates the organismal biological processes with environmental day and night cycle. This 24-hour rhythm is exhibited in every cell in the organism and is generated by the molecular clock circuitry that comprises transcriptional and translational feedback loops. While loss of circadian rhythm or alteration of clock gene expression is broadly observed in human cancers, the molecular basis underlying these perturbations and their functional implications are poorly understood. MYC oncogene is amplified in more than half of the human cancers. Its encoded protein, MYC, is a transcription factor that binds to the E- box sequence (5’-CACGTG-3’), which is the identical binding site of the master circadian transcription factor CLOCK::BMAL1. Thereby we hypothesized that deregulated circadian rhythm in cancer cells is a consequence of perturbation of E-box- containing clock genes by ectopically overexpressed MYC. In this thesis, we provide evidence that MYC or N-MYC activation alters expression of E-box-containing clock genes including PER1, PER2, REV-ERBα, REV- ERBβ and CRY1 in cell lines derived from human Burkitts lymphoma, human osteosarcoma, mouse hepatocellular carcinoma and human neuroblastoma. MYC activation also significantly suppress the expression and oscillation of the circadian transcription factor BMAL1. Although public available MYC ChIP-seq data suggest that MYC directly binds to the promoter of PER1, PER2, REV-ERBα, REV-ERBβ and CRY1 in U2OS cells, only silencing of REV-ERBα and REV-ERBβ is able to rescue BMAL1 suppression by MYC. -
Circadian Rhythms and Sleep in Drosophila Melanogaster
| FLYBOOK NERVOUS SYSTEM AND BEHAVIOUR Circadian Rhythms and Sleep in Drosophila melanogaster Christine Dubowy* and Amita Sehgal†,1 *Cell and Molecular Biology Graduate Group, Biomedical Graduate Studies, Perelman School of Medicine, and yChronobiology Program, Howard Hughes Medical Institute (HHMI), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 ORCID IDs: 0000-0002-6992-4952 (C.D.); 0000-0001-7354-9641 (A.S.) ABSTRACT The advantages of the model organism Drosophila melanogaster, including low genetic redundancy, functional simplicity, and the ability to conduct large-scale genetic screens, have been essential for understanding the molecular nature of circadian (24 hr) rhythms, and continue to be valuable in discovering novel regulators of circadian rhythms and sleep. In this review, we discuss the current understanding of these interrelated biological processes in Drosophila and the wider implications of this research. Clock genes period and timeless were first discovered in large-scale Drosophila genetic screens developed in the 1970s. Feedback of period and timeless on their own transcription forms the core of the molecular clock, and accurately timed expression, localization, post-transcriptional modification, and function of these genes is thought to be critical for maintaining the circadian cycle. Regulators, including several phosphatases and kinases, act on different steps of this feedback loop to ensure strong and accurately timed rhythms. Approximately 150 neurons in the fly brain that contain the core components of the molecular clock act together to translate this intracellular cycling into rhythmic behavior. We discuss how different groups of clock neurons serve different functions in allowing clocks to entrain to environmental cues, driving behavioral outputs at different times of day, and allowing flexible behavioral responses in different environmental conditions. -
SRBR 2010 Program Saturday, May 22, 2010 7:00–9:00 Pm Opening
SRBR 2010 Program Saturday, May 22, 2010 7:00–9:00 pm Opening reception Sunday, May 23, 2010 8:30–10:30 am Symposium 1–Transcriptional Regulation of Circadian Clocks Chair: Stacey Harmer, University of California, Davis 8:30 The molecular mechanism of photoadaptation and light entrainment of the Neurospora clock Michael Brunner, Heidelberg University 9:00 Novel approaches for studying circadian transcription in cells and organs Ueli Schibler, University of Geneva 9:30 Molecular mechanism of the drosophila clock Amita Sehgal, HHMI/University of Pennsylvania School of Medicine 10:00 Identification of a new circadian component using data mining Stacey Harmer, University of California, Davis Symposium 2–Circadian Neural Networks Chair: Fernanda Ceriani, Leloir Institute Foundation-Buenos Aires 8:30 CRYPTOCHROME is a cell autonomous neuronal blue light sensor that rapidly regulates neuronal firing rate Todd Holmes, University of California, Irvine 9:00 Accessing neural connectivity in the Drosophila circadian clock network Orie Shafer, University of Michigan 9:30 Complex Electrical States of SCN Neurons Hugh Piggins, University of Manchester 10:00 A parallel circadian system: Making sense of olfactory clocks Erik Herzog, Washington University 10:30–11:00 am Refreshment Break 11:00 am–12:30 pm Slide Session A Chair: Martin Ralph, University of Toronto 11:00 1 • USP2, a de-ubiquitinating enzyme, directly regulates BMAL1 stability and sensitivity to early evening light Heather Scoma, CBNA, Medical College of Wisconsin, Milwaukee, Wisconsin, United States 11:15 2 • The deubiquitinating enzyme USP2 is involved in the regulation of circadian rhythms Adeline Rachalski, Laboratory of Molecular Chronobiology, Douglas Mental Health Institute, Montréal, Canada 11:30 3 • Circadian rhythms in astrocytes depend on intercellular interactions and connexin 43 Luciano Marpegan, Biology, Washington University, St. -
Circuitry Underlying Sleep in Drosophila Melanogaster: Anatomy and the Role of Octopamine
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2010 Circuitry Underlying Sleep in Drosophila Melanogaster: Anatomy and the Role of Octopamine Amanda J. Crocker University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Behavioral Neurobiology Commons, and the Systems Neuroscience Commons Recommended Citation Crocker, Amanda J., "Circuitry Underlying Sleep in Drosophila Melanogaster: Anatomy and the Role of Octopamine" (2010). Publicly Accessible Penn Dissertations. 1561. https://repository.upenn.edu/edissertations/1561 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1561 For more information, please contact [email protected]. Circuitry Underlying Sleep in Drosophila Melanogaster: Anatomy and the Role of Octopamine Abstract Almost 20 years ago, the gene underlying fatal familial insomnia was discovered, first suggesting the concept that a single gene can regulate sleep. In the two decades since, there have been many advances in the field of behavioral genetics, but it is only in the past 10 years that the genetic analysis of sleep has emerged as an important discipline. Major findings include the discovery of a single gene underlying the sleep disorder narcolepsy, and identification of loci that make quantitative contributions to sleep characteristics. The sleep field has also expanded its focus from mammalian model organisms to Drosophila, zebrafish, and worms, which is allowing the application of novel genetic approaches. This thesis picks up on current sleep research to understand sleep, using Drosophila as our model organism. In Drosophila we have the unique opportunity to study at a single neuron level, how it regulates sleep and by doing this try to understand why we sleep. -
The Life and Work of Jeffrey C. Hall, Michael Rosbash, and Michael W
Binghamton University The Open Repository @ Binghamton (The ORB) Library Scholarship University Libraries Winter 1-15-2018 Analysis for Science Librarians of the 2017 Nobel Prize in Physiology or Medicine: The Life and Work of Jeffrey C. Hall, Michael Rosbash, and Michael W. Young Neyda V. Gilman [email protected] Follow this and additional works at: https://orb.binghamton.edu/librarian_fac Part of the Biochemistry Commons, Genetics and Genomics Commons, and the Library and Information Science Commons Recommended Citation Gilman, N. V. (2018). Analysis for science librarians of the 2017 Nobel Prize in Physiology or Medicine: The life and work of Jeffrey C. Hall, Michael Rosbash, and Michael W. Young. Science & Technology Libraries, , 1-26. doi:10.1080/0194262X.2017.1412848 This Article is brought to you for free and open access by the University Libraries at The Open Repository @ Binghamton (The ORB). It has been accepted for inclusion in Library Scholarship by an authorized administrator of The Open Repository @ Binghamton (The ORB). For more information, please contact [email protected]. Analysis for Science Librarians of the 2017 Nobel Prize in Physiology or Medicine: The Life and Work of Jeffrey C. Hall, Michael Rosbash, and Michael W. Young Jeffrey C. Hall, Michael Rosbash, and Michael W. Young are the 2017 Nobel Prize in Physiology or Medicine Laureates, having earned the award for their “discoveries of molecular mechanisms controlling the circadian rhythm.” They identified the genes involved in the circadian rhythm mechanism and explained how all of the different pieces of the mechanism work together. These discoveries explain how the biological cycles of Earth’s organisms correspond to the rotation of the planet, acting as an inner clock. -
Around the Clock.Scientists Want to Know How Living Cells Keep Time And
Around the Clock. Scientists want to know how living cells keep time and what these circadian rhythms mean for human health. by sarah c.p. williams illustration by michael kirkham Around the Clock. Scientists want to know how living cells keep time and what these circadian rhythms mean for human health. 14 Spring 2014 / HHMI Bulletin Circadian cycles in mammalian cells are the focus of Joseph Takahashi’s work. Noon The sun hangs high in the sky and shadows have all but disappeared. At Sonny Bryan’s Smokehouse in Dallas, the line of lunchtime patrons snakes out the door and the smell of Texas barbecue wafts across the parking lot. But it’s not just the smell that has everyone’s stomachs growling. Inside each waiting customer’s body, the digestive system is preparing for the midday meal. Anticipating food, hormones in the liver and stomach spike, and neurons in the brain send hunger signals throughout the body. Across the street, on the University of Texas Southwestern Medical Center campus, scientists in Joseph Takahashi’s lab can’t smell the barbecue, but they can tell that it’s the middle of the day just by glancing at their cages of mice or by measuring protein levels in cells—both cycle in predictable ways each day. Twenty years ago, Takahashi, an HHMI investigator, watched daily behavior patterns of mice to discover the frst gene—dubbed Clock—that controls the circadian rhythm in mammals. He found that healthy mice follow a 24-hour schedule of sleeping, eating, and exercising, even in steady darkness. -
Book of Abstracts
Virtual FENS Regional Meeting 2021 25-27 August 2021 Book of Abstracts Honorary Patronage of the Mayor of the City of Kraków Jacek Majchrowski Honorary Patronage of the Mayor of the City of Kraków Jacek Majchrowski Book of Abstracts WELCOME TO THE FENS REGIONAL MEETING 2021! The FRM 2021 is organized jointly by the Polish Neuroscience Society (PNS) and the Lithua- nian Neuroscience Association (LNA) under the auspices and with support from the Federation of the European Neuroscience Societies (FENS), and also with support from the International Brain Research Organization Pan-Europe Regional Committee (IBRO PERC). The FRM 2021 original city venue was Krakow, however, due to the COVID-19 pandemic, the Organizing Committee decided to hold the event on-line to ensure all attendees may meet safely. The conference will present the latest developments in neuroscience research and host panel discussions on topics ranging from directions for future development to diversity issues in the academia. Traditionally, the Regional Meetings foster interactions among the researchers in the region. This year, we want to take the on-line format as an opportunity, and showcase neuroscience research in our region to the global community Be a part of the FENS Regional Meeting 2021! On behalf of the FRM Organizing and Scientific Committees, Grzegorz Hess, Osvaldas Rukšėnas, President of the Polish Neuroscience Society President of the Lithuanian Neuroscience Association The content of the abstract book and the scientific posters is the propriety of the authors. Any recording, filming, photography, screenshots or other capturing of presentations, live sessions or other events, including scientific posters and the abstract book, taking place during, or associated with, the virtual FRM 2021, is prohibited without the expressed consent of the presenter. -
Flies Come Through Again, Period
Flies come through again, period Amita Sehgal J Clin Invest. 2018;128(1):108-109. https://doi.org/10.1172/JCI97839. Viewpoint Jeffrey Hall, Michael Rosbash, and Michael Young have been awarded the 2017 Nobel Prize in Physiology or Medicine for elucidating the molecular mechanism of the circadian (~24-hour) clock. Starting with the cloning of the period (per) gene, these investigators proceeded to demonstrate how endogenous clocks are composed of transcription-translation feedback loops (TTFLs) that drive rhythms in much of physiology. Beyond their fundamental significance for understanding normal physiology, the identification of clock mechanisms has led to a deeper appreciation of the health consequences of circadian disruption. Importantly, the Nobel prize–winning discoveries were made using a Drosophila melanogaster model, underscoring yet again the power of the fruit fly for biomedical research. Most physiological processes and behaviors display changes over a 24-hour period in synchrony with the day-night cycle. Sleep, body temperature, metabolic activity, and secretion of many hormones, such as cortisol and insulin, represent but a few of the processes that are different in the morning versus the evening. These rhythms are driven by endogenous clocks that have a periodicity of approximately 24 hours, hence the name “circadian” from “circa” (about) and “dies” (day). Circadian rhythms are clearly an integral part of physiology, and disruptions in them are associated with a myriad of disorders, making it important to understand the mechanisms that generate them. A genetic basis for circadian clocks Although daily […] Find the latest version: https://jci.me/97839/pdf VIEWPOINT The Journal of Clinical Investigation Flies come through again, period Amita Sehgal Chronobiology Program, Howard Hughes Medical Institute (HHMI), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.