Wikipedia:Elizabeth Maywood

Dr. Elizabeth Maywood is an English researcher studying circadian rhythms and sleep in mice. Her studies are focused in the SCN, a small region of the brain that controls circadian rhythms.

Biography
Elizabeth Maywood was born in Leeds, England. She attained a degree in Pharmacology before going to get her PhD in biochemical endocrinology in London. She then went on to the Anatomy Department at University of Cambridge to study seaonal biology in Syrain hamsters. Since then she has moved the focus of her study to circadian rhythms and sleep.

Outside of her work, Elizabeth Maywood is a fan of Leeds United and Yorkshire cricket.

Translational switching of Cry1 protein expression confers reversible control of circadian behavior in arrhythmic Cry-deficient mice
The goal of this experiment is to control the Cry1 and Cry2 proteins, responsible for proper functioning of transcriptional-translational negative feedback loops (TTFLs). To do so, 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 medium containing ncAA, the TTFLs genetically activated immediately and the strength of activation was dependent upon the dose of ncAA in the growth medium. As soon as the ncAA medium was removed, TTFL activation disappeared. Therefore, Maywood and colleagues were able to demonstrate that within the SCN, Cry1 is necessary for circadian functioning, however rhythmicity is controlled by initiation of TTFL functioning. Lastly, the paper was able to conclude that the circuit, cell, and animalian mechanisms required for circadian functioning are developmentally independent of the presence of Cry proteins.

The molecular clockwork of the suprachiasmatic nucleus is sufficient to co-ordinate phasing and stabilisation of sleep-wake cycles and enhance memory deficits in a clockless mouse
In this experiment, Dr. Maywood and her colleagues aimed to further investigate the contribution of the suprachiasmatic nucleus (SCN) and the local clocks in regulating sleep in mice. More specifically, this study was looking at whether they would be able to restore normal circadian rhythms of sleep in clockless Cryptochrome1 (Cry1/Cry2) null mice using the mediated genetic complementation expressing Cry1 in the SCN. The results revealed that for the rest and activity behavior, SCN control mice showed arrhythmicity patterns whereas the Cry1-complemented mics showed circadian behavior similar to wild-type mice. Using electroencephalography to measure sleep and wake behavior, they also found that the SCN control mice lacked circadian organization and showed more wake-NREM-wake transition. On the other hand, Cry1-complemented mice again showed circadian behavior similar to wild type mice with vigilance state including wake, REM, and NREM sleep with expression of REM within total sleep. Lastly, they found that SCN control mice showed poor sleep-dependent memory whereas Cry1-complemented mice showed corrected sleep dependent memory. All these findings showed clear restoration of circadian rhythm in clockless mice who underwent the genetic complementation. Dr. Maywood and colleagues concluded that the SCN clock is sufficient for circadian control of sleep-wake, facilitating initiation and maintenance of wake, promoting sleep consolidation, homeostatic dynamics, and sleep dependent memory.

Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory
Elizabeth Maywood and her colleagues have also studied interactions between the suprachiasmatic nucleus (SCN) and 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’s group conducted a study comparing 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 chimeric mice were temporally misaligned.source

When measuring the quality of sleep for the mice through several parameters, Maywood’s group found 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, all found 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.source

While the specific contributions of local clocks across the brain remain, 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 influences overall sleep quality.

Synchronization and maintenance of circadian timing in the mammalian clockwork
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 colleagues have 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.

Furthermore, 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 a distinctive property of spontaneous synchronization of inter-neuronal molecular timekeeping through the use of neuropeptidergic signaling.

Other works
Mayfield has also been a major contributor on the following papers:


 * Cell-autonomous clock of astrocytes drives circadian behavior in mammals
 * Circadian Rhythms: Per2bations in the Liver Clock
 * The Cell-Autonomous Clock of VIP Receptor VPAC2 Cells Regulates Period and Coherence of Circadian Behavior
 * The cell-autonomous clock of VIP receptor VPAC2 cells drives circadian behaviour

Awards
In 2011, Maywood won the Aschoff's Rule prize