The Molecular Genetics of Circadian Rhythms and Sleep

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.

e-mail Dr. Allada
ph: 847.491.2809
fax: 847.491.5211

Selected References:

• Kilman VL, Zhang L, Meissner RA, Burg E, Allada R. (2009). Perturbing dynamin reveals potent effects on the Drosophila circadian clock. PLoS ONE. 4(4):e5235. Epub 2009 Apr 22.

• Chung BY, Kilman VL, Keath JR, Pitman JL, Allada R. (2009). The GABA(A) Receptor RDL Acts in Peptidergic PDF Neurons to Promote Sleep in Drosophila. Curr Biol. 19(5):386-90.

• Allada R. (2008). How flies time when they're having brunch. Cell Metab. 8(4):279-80.

• Meissner RA, Kilman VL, Lin JM, Allada R. (2008).
TIMELESS is an important mediator of CK2 effects on circadian clock function in vivo. J Neurosci. 24;28 (39):9732-40. [Full Text].

• Allada R, Siegel JM. (2008). Unearthing the phylogenetic roots of sleep. Current Biology. 18(15):R670-9. [Full text].

• Smith EM, Lin JM, Meissner RA, Allada R. (2008). Dominant-negative CK2alpha induces potent effects on circadian rhythmicity. PLoS Genetics. 4(1):e12.

• Keegan KP, Pradhan S, Wang JP, Allada R. (2007). Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes. PLoS Computational Biology. 3(11):e208.

• Lim C, Chung BY, Pitman JL, McGill JJ, Pradhan S, Lee J, Keegan KP, Choe J, Allada R. (2007).
Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Current Biology. 17(12):1082-9.

• Allada R. (2007). Two oscillators are better than one: a circadian pacemaker escapes from the light. Neuron. 2007 53(5):621-3. [Full Text].

• Bose A, Kahali B, Zhang S, Lin JM, Allada R, Karandikar U, Bidwai AP. (2006). Drosophila CK2 regulates lateral-inhibition during eye and bristle development. Mechanisms of Development. 123(9):649-64.

• 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.

• Lear BC, Lin JM, Keath JR, McGill JJ, Raman IM, Allada R. (2005). The ion channel narrow abdomen is critical for neural output of the Drosophila circadian pacemaker. Neuron. 48(6):965-76. [Full Text].

• Lin JM, Schroeder A, Allada R. (2005). In vivo circadian function of casein kinase 2 phosphorylation sites in Drosophila PERIOD. Journal of Neuroscience. 25(48):11175-83.

• Lear BC, Merrill CE, Lin JM, Schroeder A, Zhang L, Allada R. (2005). A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior. Neuron. 48(2):221-7. [Full Text].

• Zhao J, Kilman VL, Keegan K, Peng Y, Emery P, Rosbash M, and Allada R (2003).  Drosophila Clock can generate ectopic clocks.  Cell (In press).

• Lin J-M, Kilman VL, Keegan K, Paddock B, Emery-Le M, Rosbash M, and Allada R (2002). 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) [Full Text].

• Nash HA, Scott RL, Lear BC, and Allada R (2002). An Unusual Cation Channel Mediates Photic Control of Locomotion in Drosophila.  Current Biology 12, 2152-2158. [Full Text].

• Allada R., Emery P., Takahashi J., Rosbash M. 2001. Stopping Time: The genetics of fly and mouse circadian clocks. Annu. Rev. Neurosci. 24:1091-1119. [Full Text].

Other Links:

• Electrophysiology Postdoctoral Position Available