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.

Lim C, Chung BY, Pitman JL, McGill JJ, Pradhan S, Lee J, Keegan KP, Choe J, and Allada R. (2007) clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Current Biology Jun 5; [Epub ahead of print]

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

Lear BC, Lin J-M, Keath JR, McGill JM, Raman IM, and Allada R. (2005) The ion channel narrow abdomen is critical to the neural output of the Drosophila circadian pacemaker. Neuron 48: 965-976.

Lear BC, Merrill CE, Lin J-M, Schroeder A, Zhang L, and Allada R. (2005) A novel G-protein coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior. Neuron 48, 221-227 (featured on the cover)

Commentary on this paper:

• Helfrich-Forster C. (2005) PDF has found its receptor. Neuron 48: 161-169.
• Holmes TC, Sheeba V. (2005) Circadian pathway: the other shoe drops. Curr Biol. 15:R987-9.

Zhao J, Kilman VL, Keegan KP, Ping Y, Emery P, Rosbash M, and Allada R (2003). Drosophila Clock can generate ectopic circadian clocks. Cell 113, 755-766.

Commentary on this paper:

• Hastings MH. (2003) Circadian clocks: self-assembling oscillators? Current Biology 13, R681-R682.
• Campbell N. (2003) Clockwork conductor. Nature Reviews Genetics 4, 578.
• Pilcher HN. (2003) Flies get rhythm. Nature 423, 935.

Lin J-M, Kilman VL, Keegan K, Paddock B, Emery-Le M, Rosbash M, and Allada R. A Role for Casein Kinase 2a in the Drosophila Circadian Clock. Nature 420, 816-820. Advance online publication, 24 November 2002 (doi:10.1038/nature01235)

Commentary on this paper:

• Blau J. (2003) A new role for an old kinase: CK2 and the circadian clock. Nature Neurosci 6, 208-210.

View all publications by publications by Ravi Allada listed in the National Library of Medicine (PubMed).