Blog: Showcasing DC Area Research

Every season, we cover a local area (Washington DC, Northern Virginia, Maryland) lab, research group or scientist to highlight and promote DMV area neuroscience research

September 2016

posted Sep 28, 2016, 11:11 AM by SfN DCMA   [ updated Sep 28, 2016, 11:13 AM ]

On Fruit Flies and Human Sleep: The Wu Lab at Johns Hopkins University

By Benjamin Bell and Sonia Bansal




















Dr. Mark Wu, 

MD. PhD.,

Lab Director




Benjamin Bell,
Graduate Student

            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






Not only is the lab highly productive and engaged in the work they do, members of the lab group also engage in a number of social events together and have in-lab prizes to the victors, such as a month reprieve from lab-cleaning duties, or fly flipping for a certain number of stocks!








March 2016

posted Mar 28, 2016, 1:39 PM by SfN DCMA   [ updated Mar 28, 2016, 11:00 PM ]

Navigating the Brain Forest: Center for Neural Informatics, Structures, and Plasticity, Krasnow Institute for Advanced Study, George Mason University
by Sonia Bansal
      In this era of the large-scale brain initiative, cataloguing of the brain’s building blocks, neurons, is one of the most fundamental efforts to be undertaken. Our brains can be considered as a dense forest consisting of around 100 billion neurons-the ‘trees’. These neuron trees share a basic structure consisting of ‘roots’, ‘trunk’ and ‘branches’, but are not exactly similar, and in fact have an astonishing diversity that leaves scientists with much to discover. One local DC area research group that is a frontrunner in these efforts is the Center for Neural Informatics, Structures, and Plasticity (CN3) at the Krasnow Institute for Advanced Study of George Mason University, led by Dr. Giorgio Ascoli.
     Rubén Armañanzas, research assistant professor, and IT project manager, emphasizes the need for a repository that catalogues these complex branching shapes of neurons, and this is precisely what Dr. Ascoli and his group set out to do. The group is specifically interested in the description and generation of dendritic morphology, and in its effect on neuronal electrophysiology.”  Eventually, they aim to create mega-scale, structurally plausible neural networks to model entire portions of a mammalian brain and share it on the NeuroMorpho.org platform. Since being launched in 2006, this resource has been well appreciated by the research community: “A historic database…the way modern science should proceed” (Luciano Costa, Prof., Sao Paulo Univ., Sao Carlo, Brazil); “Pure dynamite—neuroinformatics made real (Ted Carnevale, Senior Scientist, Yale Univ., New Haven, CT).
    Dr. Armañanzas explains that over the past ten years, the group has progressed in leaps and bounds in providing free 3D digital reconstructions of over 35,000 neurons from dozens of species and brain regions and continues to grow, making it the largest collection of these data (version 6.3 was released on 03/04/2016 and contains 37712 neurons). The group combines various research areas including computational neuroscience, bioinformatics and experimental neuroscience in order to collect neurons traced from studies in microscopy imaging, pharmacology, and development. The data obtained can then be utilized for additional purposes such as brain function modeling.  Dr. Armañanzas himself blends his background in computational methods and machine learning with his interest in biology to apply these techniques to gain more knowledge to digitally reconstruct neurons and to “unveil key aspects of neuronal morphogenesis in the developing brain”.  He applies information about morphological, physiological, and molecular properties to enhance efforts in automating neuronal classification using robust machine learning techniques. When asked about the favorite aspect of his involvement in this area, he says, “I’d like to think I am a little ant working in a scientific nest, adding my little work everyday to grow something bigger. I like that the research has a broader impact and is open to the public”. One additional goal of the CN3 is to develop “an ecosystem of sharing resources” by working with other initiatives such as BigNeuron (http://alleninstitute.org/bigneuron/about/), BrainInfo(http://braininfo.rprc.washington.edu/) and NEURON (http://www.neuron.yale.edu/neuron/) for the purpose of data mining, education, and outreach. There are very clear-cut de facto policies for sharing resources, and all shared work is cited, with full credit to original authors. Dr. Armañanzas notes that, although initially people from the science community were still reluctant to share data without direct profit, most researchers now have a welcoming attitude towards this kind of sharing system where secondary discoveries and other positive outcomes are closely monitored.
    Another venture that Dr. Ascoli’s group is undertaking is the Hippocampome project. Along the lines of the genome project, this knowledge base is designed to cover all aspects of the hippocampus cell types, from structure and activity to function. This project also has its foundations in cataloguing neurons (within the hippocampus). One of the signature décor pieces at the Krasnow Institute at GMU is the wire sculpture of the hippocampus, “Mental Floss”. This is a network model of the hippocampus created in collaboration with a professional DC artist and two Mason students (one art major and one in neuroscience). 
   Dr. Ascoli’s passion and dedication is pervasive throughout his lab and his group’s research initiatives and tool development have had and continue to have an enormous impact on areas ranging from neurobiology to informatics.  He was recently (3-16-15) featured as an invited speaker at SfN-DC Chapter- hosted annual Neuroscience public lecture at AAAS headquarters, and he will soon (3-29-2016) be featured as the guest author in the debut of the new Mason Author Series, which will highlight significant publications of George Mason University faculty and alumni. The neuroscience community in the DMV area is proud to call this group one of its own and we look forward to hearing of more groundbreaking discoveries emanating from this group.

  Dr. Giorgio Ascoli



Parekh & Ascoli, 2013



http://neuromorpho.org/about.jsp




Top Left: Dr. Rubén Armañanzas; Top Right: Brain quilt at Krasnow Institute, George Mason University ; Bottom Left: Hippocampome project board; Bottom Right: ‘Mental Floss’ Hippocampus sculpture.

Research Group contact information:

Website: http://krasnow1.gmu.edu/cn3/
Dr. Ascoli email address: ascoli (at) gmu (dot) edu
Dr. Rubén Armañanzas: http://mason.gmu.edu/~rarmanan/











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