Why do we sleep?

Why we sleep remains one of the most enduring mysteries in science. Sleep is homeostatically regulated where the duration of wakefulness drives subsequent sleep. Here we aim to determine how waking experience is sensed to trigger sleep and how sleep restores the brain? How the circadian clock interacts with sleep homeostasis? How impaired sleep lead to human diseases such as Alzheimer’s disease?

why do we sleep?

Why we sleep remains one of the most enduring mysteries in science. Sleep is homeostatically regulated where the duration of wakefulness drives subsequent sleep. Here we aim to determine how waking experience is sensed to trigger sleep and how sleep restores the brain? How the circadian clock interacts with sleep homeostasis? How impaired sleep lead to human diseases such as Alzheimer’s disease?

Research

Nearly every organism examined, even the jellyfish that lacks a centralized nervous system, exhibits a restorative sleep-like state. While asleep, we cannot eat, mate, defend ourselves from predators or care for our young. Inadequate sleep contributes to brain disease such as Alzheimer’s and depression, and even diseases outside of the brain, such as diabetes and obesity.  Sleep is homeostatically regulated, i.e., sleep is driven by the duration and intensity of prior waking experience.  Our principal goals are to identify the neuronal and molecular components of the sleep homeostat, to understand how those components cooperate to sense and control sleep-wake state, and to reveal how molecular and neural homeostatic pathways impact brain function, health, and disease.  Our strategy employs genetic tools primarily in the fruit fly Drosophila to dissect, manipulate and monitor the homeostatic machinery. This approach builds on our research to understand the molecular basis of circadian (~24 h) behavior which have revealed sleep mechanisms conserved between invertebrates and vertebrates and incorporates work in both mice and humans.

Circadian Rhythms

Circadian clocks dictate when we wake up and when we fall asleep.  Using molecular to behavioral approaches primarily in the fruit fly  we aim to  reveal the molecular and neuronal mechanisms by which circadian clocks keep time and convey that information to control sleep/wake?  We are also determining the mechanistic role of disrupted circadian clocks in neurodevelopmental (e.g. autism) and neurodegenerative (e.g. Huntington’s disease disorders.

Sleep Homeostasis

The elusive sleep homeostat drives sleep as a function of prior wakefulness. How does the homeostat sense waking experience, trigger sleep and restore the brain to a baseline healthy state? By combining genetics, genomics, real-time imaging, and high resolution behavior analysis, we aim to identify the locus of the sleep homeostat and understand the molecular mechanisms that govern homeostat function. We are also determining how disrupted sleep can contribute to neurodegenerative disorders such as Alzheimer’s disease.

Humans: Diagnostics/Jet Lag

Disrupted sleep and circadian rhythms have been increasingly associated with neural (depression and Alzheimer’s) and even non-neural disorders (diabetes and obesity). Here we are combining RNA-sequencing with machine learning algorithms to discover biomarker signatures of sleep and circadian disorders. We are also using publicly available data to assess the effects of sleep/circadian disruption on athletic performance.

Team

Ravi Allada

Principal Investigator 

BA, University of Michigan, Ann Arbor
MD, University of Michigan, Ann Arbor

On his way to becoming a medical doctor, Ravi decided to take a year (and then two) off during medical school to do research at the NIH.  There he caught the research ”bug” and began his career-long interest in sleep, working on mechanisms of general anesthesia in the fruit fly Drosophila. After completing his M.D and a short residency in Clinical Pathology, he did his postdoctoral training with Nobel laureate Michael Rosbash, cloning the core circadian clock gene Clock in Drosophila.  He joined the faculty at Northwestern in 2000 where his lab has discovered core gears of the circadian clock, how those gears drive sleep and wake, and how those pathways are linked to neurodegenerative disease.  He applies similar approaches to reveal the molecular basis of the sleep homeostat, key to understanding the elusive function of sleep. In his spare time, he has served or is serving on various Boards including for the Society for Research on Biological Rhythms, the Sleep Research Society and the NIH Sleep Disorders Research Advisory Board.

Bridget Lear

Research Associate Professor

BS, University of California at Los Angeles
PhD, University of Chicago

As a Ph.D. student, Bridget studied nervous system development and evolution with Dr. Nipam Patel. She then moved to the field of circadian rhythms, where she has focused on understanding the neural mechanisms regulating circadian behavior. As a postdoctoral fellow (Allada lab), Bridget helped identify the receptor for the PDF neuropeptide, a critical component of clock neuron communication in Drosophila. Her postdoctoral work also established an important role for the sodium leak channel Narrow Abdomen (aka NALCN) in circadian neuron output. As a faculty member (U. of Iowa 2010-2018; Northwestern U. 2009-10, 2018-present) she has continued to study the regulation and function of the Narrow Abdomen ion channel complex in the circadian system. She has also focused on understanding the complex relationship between neuronal network communication, environmental input, and circadian behavioral output.

Yong-Kyu Kim

Research Associate Senior

BS, Sung Kyun Kwan University
PhD, City University of New York

Yong-Kyu’s research areas are multidisciplinary in behavior genetics, evolutionary biology and neurobiology; and include the evolution of mating behavior, aggressive behavior, sleep and memory. He grew up in Seoul, Korea and graduated from Sung Kyun Kwan University. Yong-Kyu moved to USA for graduate work and got a Ph.D. degree at the City University of New York, New York. He has research and teaching experience at State University of New York, University of Georgia, Emory University and Janelia Research Campus. He joined the Allada lab to investigate neural mechanisms of how sleep enhances memory using Drosophila as a model system.

Clark Rosensweig

Postdoctoral Fellow

BA, Harvard University
PhD, University of Texas Southwestern Medical Center

Clark grew up in a sleepy beach community in South Florida. After college, he dropped out of science to pursue a career in stand up comedy, then dropped out of stand up comedy to pursue a career in science. As a graduate student in Carla Green’s lab, he performed structure/function studies of the circadian repressors Cryptochrome 1 and 2 and identified a subtle structural divergence between the two with a major role in determining periodicity in the mammalian circadian clock. Clark brought his penchant for biochemistry to the Allada lab to determine why we sleep. He has subsequently become a more interesting dinner party guest.

Shiju Sisobhan

Postdoctoral Fellow

BTech, Cochin University of Science and Technology
PhD, Indraprastha Institute of Information Technology, Delhi

I grew up in the beautiful state of Kerala (India) where I received my bachelor’s and master’s degree in electronics engineering. Then I relocate to Delhi, where I did my Ph.D. in computational biology under Dr. K. Sriram. My work in Ph.D. studies focused on the mathematical modeling of the mammalian circadian rhythm. In the Allada lab, I am focusing on developing computational tools for analyzing sleep and circadian behavior of Drosophila and human being. I am also working on bioinformatics analysis on RNA seq data from sleep-deprived Drosophila.

Gregory Wesseling

Research Technologist

Masters, Grand Valley State University
Bachelors, Central Michigan University

In graduate school at GVSU, Greg dissected larval drosophila brains to investigate histamine expression in deletion mutants generated through transposon-excision mutagenesis. When Greg joined the Allada lab, he dissected adult drosophila brains to investigate PER expression. Greg now works on project ENCODE to help document where transcription factors act in the fly genome. Before graduate school, Greg spent a summer at the University of Cambridge to study evolution. In his spare time, Greg enjoys watching college football and basketball.

Aldeb Perera

Ph.D. Candidate

BS, University of Illinois at Chicago

A Belizean native, Aldeb moved to Chicago in 2013 where he completed is BS in Biochemistry at the University of Illinois at Chicago. After graduating college, Aldeb worked in Dr. Wei Qiu’s lab at Loyola University Chicago for two years investigating liver cancer, after which he began his PhD work at Northwestern University in the Fall of 2020. He joined the Allada lab the following year, where he currently uses molecular biology and omics approaches to deconvolute sleep homeostasis. Outside of lab, Aldeb serves as the president of Northwestern’s SACNAS chapter, studies classical piano at Northwestern’s Bienen School of Music, and is a member of NEIU’s Judo Club. In his free time, he enjoys videogames, time outdoors, and game nights with his siblings.

Alumni

Postdocs

  • Dr. Jack Curran
    Ph.D., University of Bristol
  • Dr. Sumit Saurabh
    Ph.D., University of Houston
  • Dr. Bart van Alphen
    Ph.D., University of Queensland
  • Dr. Dae-Sung Hwangbo
    Ph.D., University of Rochester Medical School
  • Dr. Mikhail Koksharov
    Ph.D., Moscow State University
  • Dr. Evrim Yildirim
    Ph.D., Rutgers University
  • Dr. Jongbin Lee
    Ph.D., Korea Advanced Institute of Science & Tech
  • Dr. Matthieu Flourakis
    Ph.D., University of Lille
  • Dr. Taichi Itoh
    Ph.D., Kyushu University
  • Dr. Elzbieta Kula-Eversole
    Ph.D., Brandeis University
  • Dr. Yong Yang
    Ph.D., Peking University
  • Dr. Alena Kobelkova
    Ph.D., University of South Bohemia
  • Dr. Tae Hee Han
    Ph.D., Seoul National University
  • Dr. Yong-Jae Kwon
    Ph.D., Yonsei University
  • Dr. Lane Coffee
    Ph.D., Vanderbilt University
  • Dr. Chunghun Lim
    Ph.D., Korea Advanced Institute of Science & Tech
  • Dr. Beiyi Shen
    Ph.D., Johns Hopkins University
  • Dr. Cory Pfeiffenberger
    Ph.D., UC Santa Cruz
  • Dr. Gang Liu
    Ph.D., Chinese Academy of Sciences
  • Dr. Bridget Lear
    Ph.D., University of Chicago
  • Dr. Jena Pitman
    Ph.D., Northwestern University
  • Dr. C. Elaine Smith (Merrill)
    Ph.D., Vanderbilt University
  • Dr. J.Russel Keath
    Ph.D., University of Massachusetts
  • Dr. Jui-Ming Lin
    Ph.D., Illinois Institute of Technology
  • Dr. Valerie Kilman
    Ph.D., Brandeis University

Research Technologists

  • Vanessa Hernandez
  • Michael Lin
  • Elizabeth Williamson
  • Khadijah Hamid
  • Angelina Kim
  • Jordan Robson
  • Gabrielle Watkins
  • Setong Mavong
  • Namhee Ji
  • Erin Petrik
  • Monica Villar
  • Jermaine McGill

Ph.D. Students

  • Tomas Andreani
    2014 – 2022
  • Melanie Zhang
    2015 – 2021
  • Fangke Xu
    2012 – 2019
  • Adam Seluzicki
    2007 – 2013
  • Brian Chung
    2006 – 2010
  • Luoying Zhang
    2004 – 2009
  • Rose-Anne Meissner
    2004 – 2009
  • Jena Pitman
    2002 – 2007
  • Kevin Keegan 
    2003 – 2005 (grad 2009)

Master’s Students

  • Stanley Chen, M.S.
  • Austin Wen, M.S.
  • Vanessa Hernandez, M.S.
  • Zhichun (Michael) Lin, M.S.
  • Zuoheng (Jack) Qin, M.S.
  • Keyin Li, M. Biotech
  • Nanjia Song, M. Biotech
  • Wenhao Cao, M. Biotech
  • Timothy Earl, M. Biotech
  • Ling Kai Shih, M.S.
  • Zachary Taub, M.S.
  • Anuja Ganesan, M. Biotech
  • Weichao Zhang, M. Biotech
  • Matthew Hong, M. Biotech
  • Samuel Stewart, M.S.
  • Keya Raychaudhuri, M.S.
  • Sihan Teng, M. Biotech
  • Leigh Ann Guennewig, M. Biotech
  • Daine Stevens, M.S.
  • Adam Young, M. Biotech
  • Ryan Tubman, M. Biotech
  • Kevin Oelstrom, M. Biotech
  • Tim Requarth, M.S.
  • Anup Patel, M.S.
  • Jeff Guzelian, M.S.
  • Natalie Boone, M.S.

Selected Publications

Join the Lab

The goals of the Allada laboratory are to make important discoveries in the areas of sleep and circadian rhythms and to provide engaged scientific training and an inclusive environment for a diverse group of postdoctoral fellows, graduate students, and undergraduates. To accomplish this goal, we (mentor and mentees) collaborate by proposing novel and insightful hypotheses, carefully planning and executing well-designed experiments, rigorously and quantitatively analyzing experimental results, and lastly, interpreting results in light of controls and the published literature. Ultimately, the tangible products of our collective efforts are high impact publications that communicate our findings, competitive grant proposals that provide the funding necessary to sustain our efforts, and future careers for trainees whether in academia or elsewhere.

The Allada laboratory seeks energetic and highly motivated individuals who can excel as part of a team diverse in background, training. Our research incorporates a wide range of multidisciplinary approaches including molecular (e.g., RNA sequencing, luminescence reporter imaging), cellular (e.g, connectomics, optical imaging), and behavioral (e.g., in vivo neuronal activation). Experience with molecular biology, RNA-sequencing, bioinformatics, patch clamp electrophysiology, optical imaging, and/or Drosophila highly preferred. We are moving to the University of Michigan, located in Ann Arbor, in September 2023.

Postdoctoral Fellows

Interested individuals should send a brief statement of research interests, CV, and the names of three references by email to rallada@umich.edu.

PhD Students

Prospective PhD graduate students should apply to a relevant graduate training program at University of Michigan. Enrolled students interested in organizing a rotation in the Allada Lab should contact Dr. Ravi Allada directly at rallada@umich.edu.

Undergraduates

If you are an undergraduate interested in conducting research enrolled in independent study, full-time summer research, or in lab assistance through the work study program, please email Yong-Kyu Kim at kyongkyu@med.umich.edu (research) or Greg Wesseling at gregwess@med.umich.edu (work study).

Contact us

Ravi Allada, MD

Michigan Neuroscience Institute
University of Michigan

NCRC B25-1797
2800 Plymouth Rd
Ann Arbor, MI 48109-2800

Email: rallada@umich.edu

The Allada Lab

Address:
2800 Plymouth Rd
NCRC B25-1721
Ann Arbor, MI 48109-2800

For undergrad research, contact Yong-Kyu Kim: kyongkyu@med.umich.edu

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