Elizabeth Maywood

Last updated
Elizabeth Maywood
Born
Leeds, England
Alma materUniversity of Bradford
AwardsAschoff's Rule Prize
Scientific career
FieldsChronobiology: Circadian Functions of the SCN

Elizabeth Maywood is an English researcher who studies circadian rhythms and sleep in mice. Her studies are focused on the suprachiasmatic nucleus (SCN), a small region of the brain that controls circadian rhythms.

Contents

Biography

Elizabeth Susan Maywood was born in Leeds, England. She attained a degree in Pharmacology before going on to obtain her Ph.D. in biochemical endocrinology in London. After receiving her Ph.D., in 1988 she joined Michael Hastings’ group as a postdoc in the Department of Anatomy at the University of Cambridge (now part of the Physiology, Development and Neuroscience (PDN) Department) [1] to study seasonal biology in Syrian hamsters. In 2001 she moved with Hastings to the MRC Laboratory of Molecular Biology [2] in Cambridge, where he had set up a new research group to study the molecular neurobiology of circadian rhythms. [3] Since then, she has moved the focus of her study to circadian rhythms and sleep.

Research contributions

Early research in the field of chronobiology utilizing lesion experiments has suggested that the suprachiasmatic nucleus (SCN) serves as the master circadian clock of the mammalian brain and is entrained through retinal inputs. More recently, research on the SCN has focused on the function of individual neuropeptides and their complex interactions in the scope of the SCN circuitry. [4] Research into the role of vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), arginine vasopressin (AVP), and GABA has started to paint a picture of the hierarchy of neuropeptides in the maintenance of circadian coherence in the SCN.

Maywood's research investigates the complex interactions of various neuropeptides and the role of events at the membrane in feedback loops in the SCN. Furthermore, Maywood's research also seeks to understand how different parts of the SCN coordinate rhythms and more broadly understand the interaction of the SCN with sleep. [5]

Studies of CRY1/CRY2 in the Suprachiasmatic Nucleus

In one experiment, Maywood and her colleagues in the Hastings and Chin groups at the LMB aimed to control the Cry1 and Cry2 proteins responsible for proper functioning of transcriptional-translational negative feedback loops (TTFLs). [2] [6] To do this, the researchers used orthogonal aminoacyl-tRNA synthetase/tRNA brought to the SCN by an adeno-associated virus vector (AAV). The Cry1 protein carrying the AAV vector contained noncanonical amino acids (ncAA) and an ectopic amber stop codon resulting in a silencing mutation. When arrhythmic SCN slices lacking functional Cry1 were placed on culture mediums containing ncAA the TTFLs were genetically activated immediately, and the strength of activation depended on the dose of ncAA in the growth medium. When the ncAA medium was removed, TTFL activation disappeared. From these results, Maywood and her colleagues were able to demonstrate that within the SCN, Cry1 is necessary for circadian functioning. Rhythmicity, however, was found to be controlled by initiation of TTFL functioning. Ultimately, the study's results allowed the researchers to conclude that the circuit, cell, and animalian mechanisms required for circadian functioning are developmentally independent of the presence of Cry proteins. [6]

Studies of VPAC2 in the Suprachiasmatic Nucleus

In another study, Maywood and colleagues utilized luciferase and GFP reporter genes and real-time imaging of cellular circadian gene expression across mice SCN slice cultures to investigate the role of VIPergic signaling. Through this research, Maywood and her colleagues at the Laboratory of Molecular Biology alongside Tony Harmar at the University of Edinburgh [7] demonstrated that the Vipr2 gene, which encodes the VPAC2 receptor for Vasoactive intestinal polypeptide (VIP), is necessary both for maintenance of molecular timekeeping within individual suprachiasmatic nucleus neurons and between different SCN neurons.

Additionally, Maywood and colleagues have demonstrated that gastrin-releasing peptide (GRP), another SCN neuropeptide, can act as an enhancer and aid in synchronization of molecular timekeeping in the absence of VIPergic signals. This effect, however, is limited and insufficient to maintain coordinated molecular cycles for longer periods of time.

Maywood's research in this area has provided key insights into the SCN clockwork and how events at the membrane assist in driving intracellular feedback loops. These findings also indicate that the SCN has the distinctive property of spontaneous synchronization of inter-neuronal molecular timekeeping through the use of neuropeptidergic signaling. [8]

Studies of Interaction between Suprachiasmatic Nucleus and Sleep

Maywood and colleagues also study interactions between the suprachiasmatic nucleus (SCN) and extra-SCN local clocks in the brain, contributing to knowledge concerning the circadian component in the two-process model of sleep regulation.

To study the effects of interactions between the SCN and local clocks in the brain, Maywood compared various sleep parameters in three different groups of mice: 1) wild type (WT) mice with 24 hour circadian periods, 2) mutant CK1ε Tau mice having 20 hour circadian periods, and 3) chimeric CK1ε mice with dopamine 1a receptor (Drd1a) expressing cells in the SCN exhibiting 24h circadian periods and extra-SCN local clocks exhibiting 20 h periods. The difference in period between the SCN and local clocks resulted in temporal misalignment for the chimeric mice.

The results from this study showed evidence that temporal misalignment between the SCN and local clocks compromised sleep architecture and overall sleep quality for the chimeric mice. Chimeric mice saw less NREM sleep than their temporally aligned counterparts, decreased sleep recovery abilities, and increased amounts of sleep fragmentation. These were all concluded to be the result of internal desynchronization between the SCN and local clocks. Additionally, the effects of circadian misalignment on sleep architecture affected the mices’ cognitive abilities, where chimeric mice performed worse on sleep-dependent memory tasks than their counterparts. These results demonstrate the importance of temporal coherence between all clocks in the brain for maintaining effective circadian regulation of sleep. [9]

While the specific contributions of local clocks across the brain remain unknown, Maywood's research has shed light on the importance of extra-SCN clocks. These tissues play important roles in circadian sleep regulation, and coordination between these clocks and the SCN can determine overall sleep quality.

Awards

In 2011, Maywood was recognized with Aschoff's Rule prize [10]

Related Research Articles

<span class="mw-page-title-main">Circadian rhythm</span> Natural internal process that regulates the sleep-wake cycle

A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximize the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.

<span class="mw-page-title-main">Chronobiology</span> Field of biology

Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος, and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.

<span class="mw-page-title-main">Suprachiasmatic nucleus</span> Part of the brains hypothalamus

The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is the principal circadian pacemaker in mammals, responsible for generating circadian rhythms. Reception of light inputs from photosensitive retinal ganglion cells allow it to coordinate the subordinate cellular clocks of the body and entrain to the environment. The neuronal and hormonal activities it generates regulate many different body functions in an approximately 24-hour cycle.

<span class="mw-page-title-main">NPAS2</span> Protein-coding gene in the species Homo sapiens

Neuronal PAS domain protein 2 (NPAS2) also known as member of PAS protein 4 (MOP4) is a transcription factor protein that in humans is encoded by the NPAS2 gene. NPAS2 is paralogous to CLOCK, and both are key proteins involved in the maintenance of circadian rhythms in mammals. In the brain, NPAS2 functions as a generator and maintainer of mammalian circadian rhythms. More specifically, NPAS2 is an activator of transcription and translation of core clock and clock-controlled genes through its role in a negative feedback loop in the suprachiasmatic nucleus (SCN), the brain region responsible for the control of circadian rhythms.

<span class="mw-page-title-main">PER3</span> Protein and coding gene in humans

The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes. It is a circadian gene associated with delayed sleep phase syndrome in humans.

<span class="mw-page-title-main">Period circadian protein homolog 1</span> Protein-coding gene in the species Homo sapiens

Period circadian protein homolog 1 is a protein in humans that is encoded by the PER1 gene.

<span class="mw-page-title-main">Basic helix-loop-helix ARNT-like protein 1</span> Human protein and coding gene

Basic helix-loop-helix ARNT-like protein 1 or aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), or brain and muscle ARNT-like 1 is a protein that in humans is encoded by the BMAL1 gene on chromosome 11, region p15.3. It's also known as MOP3, and, less commonly, bHLHe5, BMAL, BMAL1C, JAP3, PASD3, and TIC.

Joseph S. Takahashi is a Japanese American neurobiologist and geneticist. Takahashi is a professor at University of Texas Southwestern Medical Center as well as an investigator at the Howard Hughes Medical Institute. Takahashi's research group discovered the genetic basis for the mammalian circadian clock in 1994 and identified the Clock gene in 1997. Takahashi was elected to the National Academy of Sciences in 2003.

Steven M. Reppert is an American neuroscientist known for his contributions to the fields of chronobiology and neuroethology. His research has focused primarily on the physiological, cellular, and molecular basis of circadian rhythms in mammals and more recently on the navigational mechanisms of migratory monarch butterflies. He was the Higgins Family Professor of Neuroscience at the University of Massachusetts Medical School from 2001 to 2017, and from 2001 to 2013 was the founding chair of the Department of Neurobiology. Reppert stepped down as chair in 2014. He is currently distinguished professor emeritus of neurobiology.

Michael Menaker, was an American chronobiologist who was Commonwealth Professor of Biology at University of Virginia. His research focused on circadian rhythmicity of vertebrates, including contributing to an understanding of light input pathways on extra-retinal photoreceptors of non-mammalian vertebrates, discovering a mammalian mutation for circadian rhythmicity, and locating a circadian oscillator in the pineal gland of bird. He wrote almost 200 scientific publications.

Hitoshi Okamura is a Japanese scientist who specializes in chronobiology. He is currently a professor of Systems Biology at Kyoto University Graduate School of Pharmaceutical Sciences and the Research Director of the Japan Science Technology Institute, CREST. Okamura's research group cloned mammalian Period genes, visualized clock oscillation at the single cell level in the central clock of the SCN, and proposed a time-signal neuronal pathway to the adrenal gland. He received a Medal of Honor with Purple Ribbon in 2007 for his research and was awarded Aschoff's Ruler for his work on circadian rhythms in rodents. His lab recently revealed the effects of m6A mRNA methylation on the circadian clock, neuronal communications in jet lag, and the role of dysregulated clocks in salt-induced hypertension.

Robert Y. Moore is an American neurologist with interests in disorders of biological rhythms, movement disorders, and behavioral neurology. He is credited with discovering the function of the suprachiasmatic nucleus (SCN) as the circadian clock, as well as, describing its organization. He is also credited with establishing the role of the mammalian retinohypothalamic tract (RHT) as a photic entrainment pathway. Moore cin 2017 serves as a professor of neurology, with a secondary in psychiatry and neuroscience at the University of Pittsburgh, and as co-director of the National Parkinson Foundation Center of Excellence at the University of Pittsburgh.

<span class="mw-page-title-main">John S. O'Neill</span> British biologist

John Stuart O’Neill is a British molecular and circadian biologist. O’Neill is currently a Principal Investigator at the MRC Laboratory of Molecular Biology in Cambridge, United Kingdom. His work focuses on the fundamental mechanisms that sustain circadian rhythms in eukaryotic cells.

<span class="mw-page-title-main">Michael Harvey Hastings</span> British neuroscientist

Michael Harvey Hastings is a British neuroscientist who works at the Medical Research Council MRC Laboratory of Molecular Biology (LMB) in Cambridge, UK. Hastings is known for his contributions to the current understanding of biological clocks in mammals and marine invertebrates.

Achim Kramer is a German chronobiologist and biochemist. He is the current head of Chronobiology at Charité – Universitätsmedizin Berlin in Berlin, Germany.

In the field of chronobiology, the dual circadian oscillator model refers to a model of entrainment initially proposed by Colin Pittendrigh and Serge Daan. The dual oscillator model suggests the presence of two coupled circadian oscillators: E (evening) and M (morning). The E oscillator is responsible for entraining the organism’s evening activity to dusk cues when the daylight fades, while the M oscillator is responsible for entraining the organism’s morning activity to dawn cues, when daylight increases. The E and M oscillators operate in an antiphase relationship. As the timing of the sun's position fluctuates over the course of the year, the oscillators' periods adjust accordingly. Other oscillators, including seasonal oscillators, have been found to work in conjunction with circadian oscillators in order to time different behaviors in organisms such as fruit flies.

<span class="mw-page-title-main">Sato Honma</span>

Sato Honma is a Japanese chronobiologist who researches the biological mechanisms of circadian rhythms. She mainly collaborates with Ken-Ichi Honma on publications, and both of their primary research focuses are the human circadian clock under temporal isolation and the mammalian suprachiasmatic nucleus (SCN), its components, and associates. Honma is a retired professor at the Hokkaido University School of Medicine in Sapporo, Japan. She received her Ph.D. in physiology from Hokkaido University. She taught physiology at the School of Medicine and then at the Research and Education Center for Brain Science at Hokkaido University. She is currently the director at the Center for Sleep and Circadian Rhythm Disorders at Sapporo Hanazono Hospital and works as a somnologist.

The food-entrainable oscillator (FEO) is a circadian clock that can be entrained by varying the time of food presentation. It was discovered when a rhythm was found in rat activity. This was called food anticipatory activity (FAA), and this is when the wheel-running activity of mice decreases after feeding, and then rapidly increases in the hours leading up to feeding. FAA appears to be present in non-mammals (pigeons/fish), but research heavily focuses on its presence in mammals. This rhythmic activity does not require the suprachiasmatic nucleus (SCN), the central circadian oscillator in mammals, implying the existence of an oscillator, the FEO, outside of the SCN, but the mechanism and location of the FEO is not yet known. There is ongoing research to investigate if the FEO is the only non-light entrainable oscillator in the body.

Martha Ulbrick Gillette is a chronobiologist and neurobiologist with research focusing on the effects of circadian clocks on integrative brain functions metabolism and the molecular mechanisms involved in signaling pathways. She is a fellow of the American Association for the Advancement of Science.

Martin R. Ralph is a circadian biologist who serves as a professor in the Psychology Department at the University of Toronto. His research primarily focuses on circadian rhythmicity in the fields of neuroscience, psychology, and endocrinology. His most notable work has been on the suprachiasmatic nucleus, now recognized as the central circadian pacemaker in mammals, but has also investigated circadian rhythms in the context of time, memory, and light.

References

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