The Circadian Clock  Protein Reviews

Series Editor: M. Zouhair Atassi Baylor College of Medicine Houston, Texas

For other titles published in this series, go to www.springer.com/series/6876  Urs Albrecht Editor

The Circadian Clock 

Editor Urs Albrecht Unit of Biochemistry Department of Medicine University of Fribourg 1700 Fribourg Switzerland [email protected]

ISBN 978-1-4419-1261-9 e-ISBN 978-1-4419-1262-6 DOI 10.1007/978-1-4419-1262-6 Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2009932755

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Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com) Preface

With the invitation to edit this volume, I wanted to take the opportunity to assemble reviews on different aspects of circadian clocks and rhythms. Although most con- tributions in this volume focus on mammalian circadian clocks, the historical intro- duction and comparative clocks section illustrate the importance of various other organisms in deciphering the mechanisms and principles of circadian . Circadian rhythms have been studied for centuries, but only recently, a molecu- lar understanding of this process has emerged. This has taken research on circadian clocks from mystic phenomenology to a mechanistic level; chains of molecular events can describe phenomena with remarkable accuracy. Nevertheless, current models of the functioning of circadian clocks are still rudimentary. This is not due to the faultiness of discovered mechanisms, but due to the lack of undiscovered processes involved in contributing to circadian rhythmicity. We know for example, that the general circadian mechanism is not regulated equally in all tissues of mam- mals. Hence, a lot still needs to be discovered to get a full understanding of circa- dian rhythms at the systems level. In this respect, technology has advanced at high speed in the last years and provided us with data illustrating the sheer complexity of regulation of physiological processes in organisms. To handle this information, computer aided integration of the results is of utmost importance in order to dis- cover novel concepts that ultimately need to be tested experimentally. In this devel- opment of new concepts lies the chance to understand living organisms better and to develop strategies to apply these new concepts for the benefit of society. A decade ago, the influence of changing day-night cycles (e.g. jet-lag and shift work) on health was intuitively possible but not taken very seriously due to lack of con- vincing scientific evidence. This has changed in the last years due to discoveries illustrating the involvement of clock components in the development of cancer, obesity and mood disorders. The main task of the circadian clock is to optimize an organism’s performance and tune it with temporal changes in the environment. In that sense, the clock links the genetic setting of the organism with its environment. A better under- standing of the circadian clock, therefore, will open avenues for treatment of diseases via environmental stimuli such as light. The importance of this approach is evident in the treatment of seasonal affective disorder and probably could be extended to the treatment of other neuropsychiatric disorders in the future.

v vi Preface

However, this non-pharmacological approach is strongly underrated since no direct economic benefit is evident, except for reducing costs for health care. On the other hand, pharmacological approaches to influence biochemical mecha- nisms via the circadian clock might emerge. First attempts to optimize available cancer treatments taking the temporal dimension into account, have indicated to be beneficial for patients. However, the awareness of the importance for the tim- ing of medical treatment is still very rudimentary in the medical community. I hope that the different topics described in this book illustrate the importance of the circadian clock for health, although the evidence presented is certainly not complete. The selected topics are thought as starting points for discussions and hopefully ignite new ideas and hypotheses. I thank the authors for their contributions. I also thank the series editor Dr. Zou Atassi, the publisher, and the various funding agencies including the EUCLOCK project for making this work possible. Finally, I thank my wife Andrea and my four children for their patience and support. Fribourg, Switzerland Urs Albrecht October 2009 Contents

1 A History of Chronobiological Concepts...... 1 Serge Daan

2 Transcriptional Regulation of Circadian Clocks...... 37 Jürgen A. Ripperger and Steven A. Brown

3 Posttranslational Regulation of Circadian Clocks...... 79 Jens T. Vanselow and Achim Kramer

4 Non-image-Forming Photoreceptors...... 105 Stuart N. Peirson and Russell G. Foster

5 Circadian Clocks and Metabolism...... 115 Henrik Oster

6 Circadian Clock, Cell Cycle and Cancer...... 139 Zhaoyang Zhao and Cheng Chi Lee

7 Comparative Clocks...... 157 Martha Merrow, David Lenssen, and Till Roenneberg

8 Circadian Neural Networks...... 179 Erik D. Herzog and Paul H. Taghert

9 The Circadian Clock and the Homeostatic Hourglass: Two Timepieces Controlling Sleep and Wakefulness...... 195 Sarah Laxhmi Chellappa and Christian Cajochen

vii viii Contents

10 Clocks, Brain Function, and Dysfunction...... 229 Céline Feillet and Urs Albrecht

11 Systems Biology and Modeling of Circadian Rhythms...... 283 Thomas d’Eysmond and Felix Naef

Index...... 295 Contributors

Urs Albrecht Unit of Biochemistry, Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland [email protected] Steven A. Brown Institute of Pharmacology and Toxicology, University of Zürich, 8057 Zürich, Switzerland [email protected] Christian Cajochen Centre for , Psychiatric University Clinics, Wilhelm Kleinstrasse 27, CH-4025 Basel, Switzerland [email protected] Sarah Laxhmi Chellappa The CAPES Foundation/Ministry of Education of Brazil, Caixa Postal 365, CEP. 70359-970, Brasilia - DF, Brazil; Centre for Chronobiology, Psychiatric University Clinics, Wilhelm Kleinstrasse 27, CH-4025 Basel, Switzerland [email protected] Serge Daan Unit of Chronobiology, Centre for Life Sciences, University of Groningen, The Netherlands [email protected] Thomas d’Eysmond School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), and Swiss Institute of Bioinformatics (SIB), CH-1015 Lausanne, Switzerland [email protected] Céline Feillet Unit of Biochemistry, Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland [email protected]

ix x Contributors

Russell G. Foster Nuffield Laboratory of Ophthalmology, The John Radcliffe Hospital, University of Oxford, Level 5 and 6 West Wing, Headley Way, Headington, Oxford OX3 9DU, UK [email protected] Erik D. Herzog Department of Biology, Washington University, St. Louis, MO 63130, USA [email protected] Achim Kramer Laboratory of Chronobiology, Charité - Universitätsmedizin Berlin, [email protected] Cheng Chi Lee Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 6.200, Houston, TX 77030 [email protected] David Lenssen Unit of Chronobiology, The University of Groningen, Haren, The Netherlands Martha Merrow Unit of Chronobiology, The University of Groningen, Haren, The Netherlands [email protected] Felix Naef School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), and Swiss Institute of Bioinformatics (SIB), CH-1015 Lausanne, Switzerland [email protected] Henrik Oster Circadian Rhythms Group, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany [email protected] Stuart N. Peirson Nuffield Laboratory of Ophthalmology, The John Radcliffe Hospital, University of Oxford, Level 5 and 6 West Wing, Headley Way, Headington, Oxford OX3 9DU, UK Jürgen A. Ripperger Unit of Biochemistry, Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland [email protected] Till Roenneberg Institute of Medical Psychology, Ludwig-Maximilians-University Munich, Munich, Germany [email protected] Contributors xi

Paul H. Taghert Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, MO 63110, USA [email protected] Jens T. Vanselow Laboratory of Chronobiology, Charité - Universitätsmedizin Berlin, Germany Center for Experimental BioInformatics (CEBI), University of Southern Denmark, Odense Zhaoyang Zhao Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 6.200, Houston, TX 77030, USA [email protected]