September 2016

There are thousands of labs across the world that work on a variety of diseases and disorders that affect people in a number of ways. And these labs are doing great work to reduce the personal and societal strain of these diseases. But sleep is a universal feature, literally every human (and animal) spends approximately 1/3 of their lives asleep, and yet we still don’t understand the underlying etiology of this behavior. And importantly, we know there is a very strong correlation between sleep amount/quality and human health and performance, and millions of people across the globe suffer either acutely or chronically from sleep issues. The Wu Lab at Johns Hopkins University focuses on understanding the molecular underpinnings of sleep in order to address the hows and whys of this behavior that is clearly integral to life. In the US, nearly 30% of all workers have reported working at least one non-standard shift and these workers have significant adverse health effects including increased risk of breast cancer and cardiovascular issues. Shift workers may even be sleeping the same quantity as others in the population, but the misalignment between their circadian rhythm and the timing of their sleep clearly has a deleterious effect. Part of the Wu lab's research seeks to understand what regulation of sleep occurs via the circadian rhythm, and is there a better way for people who must perform shift work to avoid the damaging results.

The lab director, Dr. Mark Wu has worked in a sleep clinic for most of his life as an MD, and as a result he saw multiple patients with sleep disorders. . His goal in starting the lab was to better understand the two-process model of sleep regulation, in the hope of better understanding how sleep is regulated endogenously, thus allowing for development of better care and support for patients who suffer the consequences of dysregulation.

According to Benjamin Bell, a graduate student in the lab, "Sleep is such a ubiquitous behavior, across nearly the entire animal kingdom that we don’t often pause to acknowledge just how weird it is. Evolution preferred a period of quiescence with increased arousal thresholds? That seems like an easy way to get eaten. And it is so absolutely vital that being deprived for even just a couple hours will significantly reduce performance, both physically and in terms of learning and memory. I think this is an integral question that gets at the root of complex life, and how the brain operates at such a high level. And while in our lab we have specific concepts under this umbrella that we explore such as circadian and homeostatic regulation of the behavior, all of us are constantly asking, discussing, and researching the big questions of why and how such a feature came about". Ben's favorite aspect of the research is its wide applicability: "But because I actually DO the behavior I am reading about, I can always apply something new I’ve found to my own life. For example, while I always knew I’ve been a night person more than a morning person, I’ve learned what some of the common genetic variants that make up that difference are in people, and how I can slightly change my sleep hygiene or cycle in order to work with my clock, and get to work more rested (and on time)."

While conducting the sleep screen in drosophila, looking for mutants with aberrant sleep patterns, there were weekly meetings to go over the data from all the flies screened in the past week. One week, a single fly line had the reduced sleep that counted as a hit in the screen, but it also had this unique increase in sleep latency. Although this was still as early in the research as it could possibly be, two of the post-doctoral fellows in the lab, Sha Liu and Qili Liu knew as soon as they saw that particular trace that the mutation in this fly could hold the answer to a major question in understanding sleep regulation. And in fact, this trace turned out to belong to the WIDE AWAKE fly that resulted in the important Neuron paper. They commented that they knew seeing this trace was observing an important new discovery in real time. And as they move forward in their careers, they feel they have a new sense of how to latch on to an important observation when it first rears its head.

A major turning point for Dr. Mark Wu was when we first realized that the mammalian homologue of WIDE AWAKE was expressed in the mouse SCN. All his research previously had been in drosophila, and while many of the genes and behaviors were translatable to mammals, this was the first time for him a novel protein discovered in the fly seemed to have a translatable role in the mouse, in a totally undescribed way. Flies have always been a tool to make discoveries which can be worked up the ladder to humans, but here was an example of how we could use the power of fly screens and tools in the flies to directly influence a project in mice. Since then, the lab has made progress on a number of mouse projects which use data in the fly as a guiding line.

Over the past three years the lab has published in cell, neuron, and current biology. In addition, the authors of these papers have spoken at a variety of conferences from the sleep and circadian specific, to those in the broad field of neuroscience. Many labs have been excited by the work and theyare seeing an uptick in collaboration across the board since thei work touches on so many important research areas. In recent times, some of the lab's work has also gotten some good media attention, with NPR covering the exploration of which brain areas might be involved in sleep drive: 'You Are Getting Sleepy,' Said The Scientist To The Fruit Fly.

This lab is at the forefront of studying the molecular, genetic, and cellular mechanisms underlying sleep and how sleep impacts neurological diseases, and the work emanating from this innovative, highly involved group is sure to boost the impact on neurological diseases.

Lab contact information:

Website: http://www.markwulab.net/home

Dr. Mark Wu: marknwu (AT) jhmi.edu

Benjamin Bell: bbell23 (AT) jhu.edu