Molecular Genetics of Sleep and Circadian Rhythms
Our research is focused on the circadian regulation of sleep behavior using the fruit fly Drosophila and incorporates a variety of approaches including biochemistry, molecular biology, genetics, cell culture, electrophysiology, anatomy, and behavior.
Fly genetics has uncovered the molecular logic of circadian clocks. They consist of clock proteins that feed back and control their own transcription. Remarkably, highly conserved clocks exist in humans. We are interested in how these molecular networks develop. How does phosphorylation set the speed of the clock? How do these feedback loops influence neuronal activity and output?
Astonishingly, fruit flies exhibit periods of inactivity with many of the cardinal features of mammalian sleep, including homeostatic control and similar responses to drugs such as caffeine. We have identified a fly sleep center in a region of the brain also important in long-term memory known as the mushroom bodies (MB). We are interested in understanding how the circadian clock and sleep loss influence the MB, how the MB influence sleep, and what are the links between sleep and learning? Studies in the fly raise the possibility of understanding the elusive function of sleep at the molecular level.
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.
A Systems Approach Identifies Networks and Genes Linking Sleep and Stress: Implications for Neuropsychiatric Disorders. Jiang P, Scarpa JR, Fitzpatrick K, Losic B, Gao VD, Hao K, Summa KC, Yang HS, Zhang B, Allada R, Vitaterna MH, Turek FW, and Kasarskis A. Cell Reports. 2015 May 5;11(5):835-848.
Improved Statistical Methods Enable Greater Sensitivity in Rhythm Detection for Genome-Wide Data. Hutchison AL, Maienschein-Cline M, Chiang AH, Tabei SMA, Gudjonson H, Bahroos N, Allada R, and Dinner AR. PLoS Computational Biology. 2015 March 20;11(3):e1004094.
Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior. Seluzicki A, Flourakis M, Kula-Eversole E, Zhang L, Kilman V, and Allada R. PLoS Biology. 2014 March 18;12(3):e1001810.
UNC79 and UNC80, Putative Auxiliary Subunits of the NARROW ABDOMEN Ion Channel, Are Indispensable for Robust Circadian Locomotor Rhythms in Drosophila. Lear BC, Darrah EJ, Aldrich BT, Gebre S, Scott RL, Nash HA, and Allada R. PLoS ONE. 2013 November 5;8(11):e78147.
Emerging roles for post-transcriptional regulation in circadian clocks. Lim C and Allada R. Nature Neuroscience. 2013 November;16(11):1544-1550.
ATAXIN-2 Activates PERIOD Translation to Sustain Circadian Rhythms in Drosophila. Lim C and Allada R. Science. 2013 May 17;340(6134):875-879.
Cul3 and the BTB Adaptor Insomniac Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila. Pfeiffenberger C and Allada R. PLoS Genetics. 2012 October 4;8(10):e1003003.
The novel gene twenty-four defines a critical translational step in the Drosophila clock. Lim C, Lee J, Choi C, Kilman VL, Kim J, Park SM, Jang SK, Allada R, and Choe J. Nature. 2011 February 17;470(7334):399-403.
Surprising gene expression patterns within and between PDF-containing circadian neurons in Drosophila. Kula-Eversole E, Nagoshi E, Shang Y, Rodriguez J, Allada R, and Rosbash M. PNAS. 2010 July 27;107(30):13497-13502.
DN1p Circadian Neurons Coordinate Acute Light and PDF Inputs to Produce Robust Daily Behavior in Drosophila. Zhang L, Chung BY, Lear BC, Kilman VL, Liu Y, Mahesh G, Meissner R-A, Hardin PE, and Allada R. Current Biology. 2010 April 13;20(7):591-599.
Circadian Organization of Behavior and Physiology in Drosophila. Allada R. and Chung BY. Annual Review of Physiology. 2010 March;72:605-624.
The CRYPTOCHROME Photoreceptor Gates PDF Neuropeptide Signaling to Set Circadian Network Hierarchy in Drosophila. Zhang L, Lear BC, Seluzicki A, and Allada R. Current Biology. 2009 December 15;19(23):2050-2055.
View all publications by Ravi Allada listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.