CURRICULUM VITAE Joseph S. Takahashi Howard Hughes Medical
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Circadian Clock in Cell Culture: II
The Journal of Neuroscience, January 1988, 8(i): 2230 Circadian Clock in Cell Culture: II. /n vitro Photic Entrainment of Melatonin Oscillation from Dissociated Chick Pineal Cells Linda M. Robertson and Joseph S. Takahashi Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60201 The avian pineal gland contains circadian oscillators that regulate the rhythmic synthesisof melatonin (Takahashi et al., regulate the rhythmic synthesis of melatonin. We have de- 1980; Menaker and Wisner, 1983; Takahashi and Menaker, veloped a flow-through cell culture system in order to begin 1984b). Previous work has shown that light exposure in vitro to study the cellular and molecular basis of this vertebrate can modulate N-acetyltransferase activity and melatonin pro- circadian oscillator. Pineal cell cultures express a circadian duction in chick pineal organ cultures (Deguchi, 1979a, 1981; oscillation of melatonin release for at least 5 cycles in con- Wainwright and Wainwright, 1980; Hamm et al., 1983; Taka- stant darkness with a period close to 24 hr. In all circadian hashi and Menaker, 1984b). Although acute exposure to light systems, light regulates the rhythm by the process of en- can suppressmelatonin synthesis, photic entrainment of cir- trainment that involves control of the phase and period of cadian rhythms in the pineal in vitro has not been definitively the circadian oscillator. In chick pineal cell cultures we have demonstrated. Preliminary work hassuggested that entrainment investigated the entraining effects of light in 2 ways: by shift- may occur; however, none of these studies demonstrated that ing the light-dark cycle in vitro and by measuring the phase- the steady-state phase of the oscillator was regulated by light shifting effects of single light pulses. -
Faculty Mentor List Basic Science Faculty Mentors 1. Joseph
Faculty Mentor List Basic Science faculty mentors 1. Joseph Takahashi, Ph.D. Professor and Chair, Department of Neuroscience [email protected] Research Statement: The long-term goals of the Takahashi laboratory are to understand the molecular and genetic basis of circadian rhythms in mammals and to utilize forward genetic approaches in the mouse as a tool for gene discovery for complex behavior. We have focused our attention in three areas: 1) identification of circadian clock genes and assignment of their function in the molecular mechanism of the circadian pacemaker; 2) analysis of central and peripheral circadian oscillators using real-time circadian reporters; and 3) identification of genes defined by mutations isolated in the large-scale mutagenesis screens we have conducted on neural and behavioral phenotypes including psychostimulant responses and contextual and cue dependent fear conditioning. Recently, we have focused on the structural biology of circadian clock proteins and on genomewide analysis of transcription factor binding and gene expression using next generation sequencing methods. A comprehensive global analysis of circadian transcription factor binding in the mouse liver has been completed in which all core components of the clock gene pathway have been interrogated. In addition, we have also analyzed the genome-wide regulation of nascent transcription, RNA polymerase II occupancy and epigenomic regulation of chromatin by the circadian clock. We have recently identified genes involved in cocaine responsiveness using forward genetic approaches. My laboratory has demonstrated a successful record of research productivity and training in circadian biology, mammalian genetics, genomics and molecular biology. 1. Huang, N, Y Chelliah, Y Shan, CA Taylor, S-H Yoo, C Partch, CB Green, H Zhang, JS Takahashi 2012 Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex. -
Neuromedin U Directly Stimulates Growth of Cultured Rat Calvarial Osteoblast-Like Cells Acting Via the NMU Receptor 2 Isoform
363-368 1/8/08 15:53 Page 363 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22: 363-368, 2008 363 Neuromedin U directly stimulates growth of cultured rat calvarial osteoblast-like cells acting via the NMU receptor 2 isoform MARCIN RUCINSKI, AGNIESZKA ZIOLKOWSKA, MARIANNA TYCZEWSKA, MARTA SZYSZKA and LUDWIK K. MALENDOWICZ Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecicki St., 60-781 Poznan, Poland Received April 4, 2008; Accepted June 2, 2008 DOI: 10.3892/ijmm_00000031 Abstract. The neuromedin U (NMU) system is composed of nervous system. Among others, peptides involved in regulation NMU, neuromedin S (NMS) and their receptors NMUR1 and of energy homeostasis belong to this group of compounds NMUR2. This system is involved in the regulation of energy (1-3), and the best recognised is leptin, an adipocyte-derived homeostasis, neuroendocrine functions, immune response, anorexigenic hormone, which plays a role in regulating bone circadian rhythm and spermatogenesis. The present study formation. Acting directly this pleiotropic cytokine exerts a aimed to investigate the possible role of the NMU system in stimulatory effect on bone formation. While acting through regulating functions of cultured rat calvarial osteoblast-like the central nervous system (CNS) leptin suppresses bone (ROB) cells. By using QPCR, high expression of NMU formation (4-10). Moreover, OB-Rb mRNA is expressed in mRNA was found in freshly isolated ROB cells while after 7, osteoblasts, and in vitro leptin enhances their proliferation 14, and 21 days of culture, expression of the studied gene and has no effect on osteocalcin and osteopontin production by was very low. -
Importance of Circadian Timing for Aging and Longevity
REVIEW ARTICLE https://doi.org/10.1038/s41467-021-22922-6 OPEN Importance of circadian timing for aging and longevity Victoria A. Acosta-Rodríguez 1, Filipa Rijo-Ferreira 1,2, Carla B. Green 1 & ✉ Joseph S. Takahashi 1,2 Dietary restriction (DR) decreases body weight, improves health, and extends lifespan. DR can be achieved by controlling how much and/or when food is provided, as well as by 1234567890():,; adjusting nutritional composition. Because these factors are often combined during DR, it is unclear which are necessary for beneficial effects. Several drugs have been utilized that target nutrient-sensing gene pathways, many of which change expression throughout the day, suggesting that the timing of drug administration is critical. Here, we discuss how dietary and pharmacological interventions promote a healthy lifespan by influencing energy intake and circadian rhythms. ging is a major risk factor for chronic diseases, including obesity, diabetes, cancer, Acardiovascular disease, and neurodegenerative disorders1. Improvements in healthcare have increased life expectancy worldwide, but as the aged population increases, frailty and morbidity have become a public health burden. Through the Healthy Life Expectancy (HALE) indicator, the World Health Organization estimates that worldwide humans spend >10% of our lives suffering from age-related diseases. Aging research currently focuses on closing the gap between lifespan (living longer) and healthspan (remaining healthier for longer). While lifespan can be easily determined with survival curves, healthspan is more complex to quantify. Several biomarkers of healthspan are used in animal models2,3 and humans4, ranging from levels of metabolites (glucose, cholesterol, fatty acids), biological processes (inflammation, autophagy, senescence, blood pressure) to biological functions (behavior, cognition, cardiovascular perfor- mance, fitness, and frailty). -
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. -
A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons
7682 • The Journal of Neuroscience, August 17, 2005 • 25(33):7682–7686 Brief Communication A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons Gabriella B. Lundkvist,1 Yongho Kwak,1 Erin K. Davis,1 Hajime Tei,2 and Gene D. Block1 1Center for Biological Timing, Department of Biology, University of Virginia, Charlottesville, Virginia 22903, and 2Research Group of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo 194-8511, Japan Generation of mammalian circadian rhythms involves molecular transcriptional and translational feedback loops. It is not clear how membrane events interact with the intracellular molecular clock or whether membrane activities are involved in the actual generation of the circadian rhythm. We examined the role of membrane potential and calcium (Ca 2ϩ) influx in the expression of the circadian rhythm of the clock gene Period 1 (Per1) within the rat suprachiasmatic nucleus (SCN), the master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization, caused by lowering the extracellular concentration of potassium or blocking Ca 2ϩ influx in SCN cultures by lowering [Ca 2ϩ], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca 2ϩ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca 2ϩ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca 2ϩ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function. Key words: circadian rhythm; calcium; potassium; suprachiasmatic nucleus; Period 1; PERIOD 2 Introduction et al., 2002). -
Neurobiology, Endocrinology and Behavior E
Neurobiology, Endocrinology and Behavior E. Adkins-Regan, Cornell University, Ithaca, NY, USA C. S. Carter, University of Illinois at Chicago, Chicago, IL, USA ã 2010 Elsevier Ltd. All rights reserved. Introduction In subsequent centuries, many scientists examined and described the structure of the brain and nervous system Two types of mechanisms, neural and hormonal, have in an array of animal species. A common theme was to note been prominent in the history of research directed at what seemed to be marked differences in the organization uncovering the proximate physiological causes of animal of the brain, especially the forebrain, and in the relative behavior. During the first part of this history, the nervous sizes of structures and brain divisions, and to speculate and endocrine systems were envisioned as separate sys- about their relationship to behavior and intelligence. tems and were studied by somewhat different research With the publication of Charles Darwin’s theory of communities. As a result, research on physiological evolution by natural selection, these species differences mechanisms of animal behavior has tended to develop in brain structure and size began to be interpreted in an along two somewhat separate and parallel tracks. These evolutionary framework. Until the middle of the 1900s, dual origins are reflected in the organization of this sur- the dominant view had been that the brains (especially vey. Beginning in the twentieth century, several discov- forebrains) of different vertebrate classes (as represented eries led to the realization that the nervous and endocrine by a small number of species from each of the largest systems are physiologically integrated to a highly signifi- classes) were fundamentally different in organization, cant extent, which is of great importance for animal that they formed an evolutionary series progressing behavior. -
Behavioral Neurobiology Biological Rhythms
Handbook of Behavioral Neurobiology Volume 4 Biological Rhythms HANDBOOK OF BEHAVIORAL NEUROBIOLOGY General Editor: Frederick A. King Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia Editorial Board: Vincent G. Dethier Robert W. Goy David A. Hamburg Peter Marler James L. McGaugh William D. Neff Eliot Stellar Volume 1 Sensory Integration Edited by R. Bruce Masterton Volume 2 Neuropsychology Edited by Michael S. Gazzaniga Volume 3 Social Behavior and Communication Edited by Peter Marler and J. G. Vandenbergh Volume 4 Biological Rhythms Edited by Jiirgen Aschoff Volume 5 Motor Coordination Edited by Arnold L. Towe and Erich S. Luschei A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. Handbook of Behavioral Neurobiology Volume 4 Biological Rhythms Edited by Jiirgen Aschoff Max-Planck Institut fur Verhaltensphysiologie Andechs, German Federal Republic PLENUM PRESS, NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Main entry under title: Biological rhythms. (Handbook of behavioral neurobiology; v. 4) Includes index. 1. Biological rhythms. I. Aschoff, J iirgen. II. Series. QP84.6.B56 591.1'882 80-21037 ISBN 978-1-4615-6554-3 ISBN 978-1-4615-6552-9 (eBook) DOl 10.1007/978-1-4615-6552-9 © 1981 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1981 A Division of Plenum Publishing Corporation -
Different Distribution of Neuromedin S and Its Mrna in the Rat Brain: NMS Peptide Is Present Not Only in the Hypothalamus As the Mrna, but Also in the Brainstem
ORIGINAL RESEARCH ARTICLE published: 03 December 2012 doi: 10.3389/fendo.2012.00152 Different distribution of neuromedin S and its mRNA in the rat brain: NMS peptide is present not only in the hypothalamus as the mRNA, but also in the brainstem Miwa Mori 1†, Kenji Mori 1†,Takanori Ida2,Takahiro Sato3, Masayasu Kojima3, Mikiya Miyazato1* and Kenji Kangawa1 1 Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan 2 Interdisciplinary Research Organization, University of Miyazaki, Miyazaki, Japan 3 Molecular Genetics, Institute of Life Sciences, Kurume University, Fukuoka, Japan Edited by: Neuromedin S (NMS) is a neuropeptide identified as another endogenous ligand for two Hubert Vaudry, University of Rouen, orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1, which have also been France identified as types 1 and 2 receptors for neuromedin U structurally related to NMS. Although Reviewed by: expression of NMS mRNA is found mainly in the brain, spleen, and testis, the distribution of Etienne Challet, Centre National de la Recherche Scientifique, France its peptide has not yet been investigated. Using a newly prepared antiserum, we developed Manuel Tena-Sempere, University of a highly sensitive radioimmunoassay for rat NMS. NMS peptide was clearly detected in the Cordoba, Spain rat brain at a concentration of 68.3 ± 3.4 fmol/g wet weight, but it was hardly detected in the *Correspondence: spleen and testis. A high content of NMS peptide was found in the hypothalamus, midbrain, Mikiya Miyazato, Department of and pons–medulla oblongata, whereas abundant expression of NMS mRNA was detected Biochemistry, National Cerebral and Cardiovascular Center Research only in the hypothalamus. -
Biotechnology School of Biotechnology G.M
Programme Structure Post Graduate in Biotechnology School of Biotechnology G.M. University, Sambalpur Post graduate programme comprising two years, will be divided into 4 (four) semesters each of six months duration. Year Semesters First Year Semester I Semester II Second Year Semester III Semester IV The detail of title of papers, credit hours, division of marks etc of all the papers of all semesters is given below. There will be two elective groupsnamely: Discipline Specific Elective in SemII. Interdisciplinary Elective in SemIII. A student has to select one of the DSE paper in Sem II and one of the papers in Sem III as offered by the department at the beginning of the semester II and semester IIIrespectively. Each paper will be of 100 marks out of which 80 marks shall be allocated for semester examination and 20 marks for internal assessment (Mid TermExamination). There will be four lecture hours of teaching per week for eachpaper. Duration of examination of each paper shall be of threehours. Pass Percentage: The minimum marks required to pass any paper shall be 40 percent in each paper and 40 percent in aggregate of asemester. No students will be allowed to avail more than three (3) chances to pass in any paper inclusive of first attempt. Semester-1 Papers Marks Total Duration Credit Paper No Title Mid End Marks (Hrs) Hours Term Term 101 Cell & Molecular Biology 20 80 100 4 4 102 Microbiology 20 80 100 4 4 103 Biochemistry 20 80 100 4 4 104 Genetics 20 80 100 4 4 105 Lab course 100 100 4 4 Total 500 20 20 Semester-2 Papers Marks Total Duration Credit Paper Title Mid End Marks (Hrs) Hours No Term Term 201 Genetic Engineering 20 80 100 4 4 202 Instrumentation and Computer 20 80 100 4 4 Techniques 1 | P a g e 203 Biostatistics and Basics of 20 80 100 4 4 Bioinformatics 204 Developmental Biology (Plant & 20 80 100 4 4 Animal) 205 Lab course 100 100 4 4 DSEPapers* 206 A Animal Physiology 20 80 100 4 4 206 B Plant Physiology 20 80 100 4 4 206 C Bioenergetics and Metabolism 20 80 100 4 4 Total 600 24 *Discipline Specific Elective Paper. -
Neuromechanics of Coordination During Swallowing in Aplysia Californica
1470 • The Journal of Neuroscience, February 1, 2006 • 26(5):1470–1485 Behavioral/Systems/Cognitive Neuromechanics of Coordination during Swallowing in Aplysia californica Hui Ye,1 Douglas W. Morton,2 and Hillel J. Chiel1,2,3 Departments of 1Biomedical Engineering, 2Neuroscience, and 3Biology, Case Western Reserve University, Cleveland, Ohio 44106-7080 Bernstein (1967) hypothesized that preparation of the periphery was crucial for correct responses to motor output. To test this hypothesis in a behaving animal, we examined the roles of two identified motor neurons, B7 and B8, which contribute to feeding behavior in the marine mollusk Aplysia californica. Neuron B7 innervates a hinge muscle and has no overt behavioral effect during smaller-amplitude (type A) swallows, because the hinge muscle is too short to exert force. Neuron B8 activates a muscle (I4) that acts solely to grasp material during type A swallows. During larger-amplitude (type B) swallows, the behavioral actions of both motor neurons change, because the larger-amplitude anterior movement of the grasper sets up the periphery to respond differently to motor outputs. The larger anterior movement stretches the hinge muscle, so that activating neuron B7 mediates the initial retraction phase of swallowing. The changed position of the I4 muscle allows neuron B8 not only to induce grasping but also to pull material into the buccal cavity, contributing to retraction. Thus, larger-amplitude swallows are associated with the expression of two new degrees of freedom (use of the hinge to retract and use of the grasper to retract) that are essential for mediating type B swallows. These results provide a direct demonstration of Bernstein’s hypothesis that properly positioning the periphery can be crucial for its ability to correctly respond to motor output and also demonstrate that biomechanical context can alter the functions of identified motor neurons. -
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.