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 leads to human diseases such as Alzheimer’s disease?

why do we sleep?

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.

Rajesh Narasimamurthy

Assistant Research Scientist

MSc, Bharathidasan University, India
PhD, University of Zurich, Switzerland

Shannon Kincaid

Research Fellow

Farheen Akhtar

Research Fellow

BS, MS, Aligarh Muslim University, India
Ph.D., Aligarh Muslim University, India

Farheen earned her Ph.D. in Biotechnology from Aligarh Muslim University, India (2022), where she developed nanoparticle-based photodynamic therapies for multidrug-resistant infections, resulting in an Indian patent. She then pursued postdoctoral research at the University of Pennsylvania, investigating circadian rhythms and metabolic regulation in Drosophila and mouse models. After three years at Penn, she has joined the Allada Lab at the Michigan Neuroscience Institute, University of Michigan, where her work focuses on sleep homeostasis and its metabolic underpinnings. She is passionate about bridging basic biology with translational therapeutics to address complex biomedical challenges through interdisciplinary science.

Shiju Sisobhan

Research Area Specialist

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

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. Then I worked as postdoc at Northwesern University, Chicago and at University of Michigan. 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 bulk and single cell RNA sequencing data, machine learning and biomarker discovery.

Gregory Wesseling

Research Specialist, Lab Manager

MS, Grand Valley State University, Allendale
BS, Central Michigan University, Mount Pleasant

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.

Tuhin Chakraborty

Research Specialist

Ph.D., National Center for Biological Sciences (NCBS), Bangalore, India
MS, Viswa-Bharati University, Santiniketan, India

Dr. Tuhin Subhra Chakraborty is a Research Specialist at the Michigan Neuroscience Institute (MNI). He received a master’s degree in Zoology from Visva-Bharati University, Santiniketan, India and the Ph.D. in Neurobiology from the National Center for Biological Sciences (NCBS), Bangalore, India. After completing a postdoctoral fellowship in System Neuroscience at the University of California, San Diego, Tuhin joined the Department of Molecular and Integrative Physiology (MIP), University of Michigan in Ann Arbor where he uses Drosophila melanogaster as a model organism to study the impacts of severe experiences on an organism’s survival and quality of life. This is achieved through unraveling links between perception and homeostatic control.

Madison Hoogstra

Research Associate

BS, Calvin University, Grand Rapids

Maddy was born and raised near Chicago, where her passion for science first took root. She earned her B.S. in Biochemistry with a concentration in Neuroscience from Calvin University, gaining research experience through internships at both Calvin and the Van Andel Institute. After graduating, she joined the Allada Lab, where she applies molecular biology approaches to study sleep homeostasis in Drosophila. Outside the lab, Maddy can be found hiking, baking, rock climbing, or spending time with friends and family.

Aadish Mithil Shah

Associate Data Scientist

BSE Data Science, University of Michigan, Ann Arbor (c/o 2021)

Aadish was born and raised in Bahrain but is of Indian descent. After moving to the US in 2017, he completed my BSE in data science eng. at UMich, unofficially focusing in AI, ML and computational methods. After graduating in 2021, he spent three years building a social networking startup, launching 8 software products, fueled by pre-seed funding secured through the Desai Accelerator program- an entrepreneurship investment arm of the Zell Lurie Institute at the Ross School of Business. At the Allada Lab, Aadish leverages his data science and entrepreneurial experience to develop data applications that analyze fly scRNA/bulk RNA seq transcriptomics, model fly behavior, and automate experiments. His fascination with sleep and its profound impact on biology, inspired by personal experience, has deepened through his work at the Allada Lab, where he is driven to better understand the science behind why we sleep. Aside from work, Aadish also enjoys preparing meals for family & friends, playing the guitar and watching soccer games (especially when Chelsea is winning.)

Alumni

Postdoctoral Fellows

Jordan Munroe Ph.D., University of Oregon

Clark Rosensweig Ph.D., UT Southwestern Medical Center

Jack Curran Ph.D., University of Bristol

Sumit Saurabh Ph.D., University of Houston

Bart van Alphen Ph.D., University of Queensland

Dae-Sung Hwangbo Ph.D., University of Rochester Medical School

Mikhail Koksharov Ph.D., Moscow State University

Evrim Yildirim Ph.D., Rutgers University

Jongbin Lee Ph.D., Korea Advanced Institute of Science & Tech

Matthieu Flourakis Ph.D., University of Lille

Taichi Itoh Ph.D., Kyushu University

Elzbieta Kula-Eversole Ph.D., Brandeis University

Yong Yang Ph.D., Peking University

Alena Kobelkova Ph.D., University of South Bohemia

Tae Hee Han Ph.D., Seoul National University

Yong-Jae Kwon Ph.D., Yonsei University

Lane Coffee Ph.D., Vanderbilt University

Chunghun Lim Ph.D., Korea Advanced Institute of Science & Tech

Beiyi Shen Ph.D., Johns Hopkins University

Cory Pfeiffenberger Ph.D., UC Santa Cruz

Gang Liu Ph.D., Chinese Academy of Sciences

Bridget Lear Ph.D., University of Chicago

Jena Pitman Ph.D., Northwestern University

C. Elaine Smith (Merrill) Ph.D., Vanderbilt University

J.Russel Keath Ph.D., University of Massachusetts

Jui-Ming Lin Ph.D., Illinois Institute of Technology

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 (Leung)
2002 – 2007

Kevin Keegan
2003 – 2005

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 (Kowalski), M. Biotech

Diane 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 (Kim), M.S.

Selected Publications

For Complete Publication List View on Google Scholar

Shiju Sisobhan, Clark Rosensweig, Bridget C Lear, Ravi Allada, SleepMat: a new behavioral analysis software program for sleep and circadian rhythms, Sleep, Volume 45, Issue 12, December 2022, zsac195, https://doi.org/10.1093/sleep/zsac195

Andreani T, Rosensweig C, Sisobhan S, Ogunlana E, Kath W, Allada R (2022). Circadian programming of the ellipsoid body sleep homeostat in Drosophila. Elife. 11:e74327. doi: 10.7554/eLife.74327.

Zhang MY, Lear BC, Allada, R (2022). The microtubule-associated protein Tau suppresses the axonal distribution of PDF neuropeptide and mitochondria in circadian clock neurons. Human Molecular Genetics. doi: 10.1093/hmg/ddab303.

Van Alphen B, Stewart S, Iwanaszko M, Xu F, Li K, Rozenfeld S, Ramakrishnan A, Itoh TQ, Sisobhan S, Qin Z, Lear BC, Allada R (2022). Glial immune-related pathways mediate effects of closed head traumatic brain injury on behavior and lethality in Drosophila. PLoS Bio. doi: 10.1371/journal.pbio.3001456.

Xu F, Kula-Eversole E, Iwanaszko M, Hutchison AL, Dinner A, Allada R (2019). Circadian Clocks Function in Concert with Heat Shock Organizing Protein to Modulate Mutant Huntingtin Aggregation and Toxicity. Cell Rep. 27(1):59-70.e4. doi: 10.1016/j.celrep.2019.03.015 (Featured on the Cover).

Braun R, Kath WL, Iwanaszko M, Kula-Eversole E, Abbott SM, Reid KJ, Zee PC, Allada R (2018). Universal Method for Robust Detection of Circadian State from Gene Expression. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.1800313115.

Song A, Severini T, Allada R. (2017). How Jet Lag Impairs Major League Baseball Performance. Proc Natl Acad Sci U S A. 114(6): 1407-1412. Doi: 10.1073/pnas.1608847114

Flourakis M, Kula-Eversole E, Hutchison, AL, Han T, Aranda, K, Moose, DL, White KP, Dinner AR, Lear, BC, Ren D, Diekman, C, Raman IM, Allada R. (2015). A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability. Cell. 162(4): 836-848.

Commentary on this paper:

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Lim C and Allada R. ATAXIN-2 activates PERIOD translation to sustain circadian rhythms in Drosophila (2013). Science. 340(6134):875-9. doi: 10.1126/science.1234785.

Pfeiffenberger C, Allada R. Cul3 and the BTB Adaptor Insomniac Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila (2012). PLoS Genetics. 8(10):e1003003.

Pitman JL, McGill JJ, Keegan KP, Allada R. (2006). A dynamic role for the mushroom bodies in promoting sleep in Drosophila. Nature. 441(7094):753-6.

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 and 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.

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

Undergraduates interested in research—whether for independent study, full-time summer research, or lab assistance through the work-study program—should email Greg Wesseling at gregwess@med.umich.edu.

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 Greg Wesseling: gregwess@med.umich.edu

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