Ravi Allada Molecular genetics of circadian rhythms and sleep

Research Interests

One of the most fundamental and enduring mysteries in all of science is why we sleep. We spend roughly one-third of our lives in this immobile, unconscious, and unresponsive state. While asleep, we can’t eat, mate, defend ourselves from predators or care for our young.  Tens of millions of Americans suffer from inadequate sleep contributing to diseases from depression and Alzheimer’s disease to diabetes and obesity. Yet we still lack a mechanistic understanding of why we sleep.   

Sleep is governed by a homeostat that drives sleep as a function of duration of prior wakefulness and a circadian clock that time sleep and wake on a daily schedule. The mechanistic basis of the sleep homeostat remains unclear, i.e., how the homeostat senses waking signals, how the homeostat triggers sleep, and how sleep promotes optimal brain function and protects against neurodegenerative diseases such as Alzheimer’s. While my lab and others have discovered molecular gears of the clock, how these gears time sleep and wake is also poorly understood. To address these questions, my laboratory is primarily using molecular neurogenetics in the fruit fly Drosophila. The fly exhibits a remarkably complex neurobehavioral repertoire, including all of the hallmarks of sleep: immobility, unresponsiveness, homeostatic responses to sleep loss (including impaired memory consolidation), and shared responses to sleep-regulating compounds such as caffeine. To address these questions, we employ molecular genetics, RNA-sequencing, electrophysiology, optical imaging, quantitative behavioral assays, and computational methods and have extended our work in flies to mice and humans.

Selected Publications

Circadian Clocks Function in Concert with Heat Shock Organizing Protein to Modulate Mutant Huntingtin Aggregation and Toxicity. Xu F, Kula-Eversole E, Iwanaszko M, Hutchison AL, Dinner A, and Allada R. Cell Reports. 2019 April 2;27(1):59-70.

Universal method for robust detection of circadian state from gene expression. Braun R, Kath WL, Iwanaszko M, Kula-Eversole E, Abbott SM, Reid KJ, Zee PC, and Allada R. PNAS. 2018 September 25;115(39):E9247-E9256.

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability. Flourakis M, Kula-Eversole E, Hutchison AL, Han TH, Aranda K, Moose DL, White KP, Dinner AR, Lear BC, Ren D, Diekman CO, Raman IM, and Allada R. Cell. 2015 August 13;162(4):836-848.

ATAXIN-2 Activates PERIOD Translation to Sustain Circadian Rhythms in Drosophila. Lim C and Allada R. Science. 2013 May 17;340(6134):875-879.

A dynamic role for the mushroom bodies in promoting sleep in Drosophila. Pitman JL, McGill JJ, Keegan KP, and Allada R. Nature. 2006 June 8;441(7094):753-756.

View all publications by Ravi Allada listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.