Ravi Allada (born 1967) is an Indian-American chronobiologist studying the circadian and homeostatic regulation of sleep primarily in the fruit fly Drosophila. He is the Edward C. Stuntz Distinguished Professor of Neuroscience and Chair of the Department of Neurobiology at Northwestern University. Working with Michael Rosbash, he positionally cloned the Drosophila Clock gene. In his laboratory at Northwestern, he discovered a conserved mechanism for circadian control of sleep-wake cycle, as well as circuit mechanisms that manage levels of sleep.
Early life
Ravi Allada was born on August 20, 1967, in Midland, Michigan, to Indian immigrant parents, Sambasiva Rao and Jayalakshmi. Allada has two brothers, Vivek and Gopal, who both currently work as physicians. At the age of 11, Allada won 3rd place in a free throw competition. Allada's interest in sports also led him to track baseball statistics, which triggered Ravi Allada’s interest in math and later, his research on jet lag for MLB players.
Education
Allada graduated from H. H. Dow High school in 1985. Following high school, Allada attended the University of Michigan where he was awarded his B.S. degree.
Allada was also awarded his M.D. by the University of Michigan. While attending University of Michigan Medical School, Allada spent two years as an HHMI-NIH Research Scholar working with Howard Nash on a molecular genetics project relating to general anesthesia in Drosophila. Before the end of medical school, he returned to NIH as a HHMI-NIH Continued Support Fellow working with Carl Wu at the NCI. Following medical school, he completed his residency in clinical pathology at Brigham and Women's Hospital in Boston. Thereafter, he completed an HHMI Physician Postdoctoral Fellowship with Michael Rosbash at Brandeis University.
Career
In 2000, Allada joined the faculty of Northwestern University, where he continues to work as a Professor and Chair of Neurobiology, a Professor and the Associate Director of the Center for Sleep and Circadian Biology. Currently, Allada also serves on the Board of Directors for the Sleep Research Society. Previously, Allada served on the NIH Sleep Disorders Research Advisory Board and on the Society for Research on Biological Rhythms Board of Directors as Secretary.
The Allada lab focuses on finding molecular components of the circadian clock and their impacts on neurodegenerative diseases, sleep, jet lag, and memory processing. His lab has begun to shift its focus to research regarding sleep homeostasis. Allada’s research has been supported financially by the NIH, the Defense Advanced Research Projects Agency, and other private foundations.
Early research
Drosophila circadian rhythms
Molecular identification of the Drosophila Clock Gene (1998) Using Drosophila melanogaster as a model organism, Allada and his team used forward genetics to discover a circadian rhythm gene called Drosophila Clock (dClock; Clk). Forward genetics screens for observable phenotypes that could potentially correspond to underlying genetic differences typically resulting from randomly induced mutagenesis. dClock (Clk) was discovered when Allada and his colleagues were completing a forward genetic screen of EMS mutagenized flies. The mutation found by Allada, that abolishes fly circadian rhythms is termed Jrk.
Functioning, CLOCK proteins encoded by the Clk gene form a dimer with CYCLE proteins. The formed dimer will bind to the E-box sequence which will activate the enhancers of per and tim genes. per and tim have been shown in Drosophila, to have daily rhythms of transcription. These per and tim mRNA transcripts are translated into proteins, PER and TIM, which heterodimerize and are essential for the circadian rhythms. The Jrk mutation within Clk, eliminates the cycling of per and tim mRNA transcripts which disrupts molecular and behavioral outputs of the circadian clock.
The studies of the Jrk mutation in the Clk gene showed dominant effects on the Drosophila. Half of the heterozygous flies demonstrate arrhythmic activity and reduce amplitude levels of per/tim transcripts in constant darkness. While all homozygous flies showed arrhythmic activity in constant darkness. Coupled with complementation data with a null deletion. Data suggests that the Jrk mutation has a negative dominant effect, meaning that only one copy of the gene is sufficient for phenotype interference. Further studies of the output of other clock proteins, namely, PERIOD (PER) and TIMELESS (TIM), showed very low expression levels.