The 2009 George W. Beadle Award: Jay C. Dunlap

Article excerpt

THE 2009 George W. Beadle Medal for outstanding contributions to the genetics community is awarded to Jay C. Dunlap. This award is a tribute to Jay's pioneering studies on the circadian clock and the Neurospora crassa frequency ( frq) gene-the first microbial clock gene to be cloned (McClung et al. 1989). Jay's work on the genetics of circadian rhythms came at a time when the field of chronobiology was still in its infancy and when the research focused primarily on the physiology and anatomy of the clock. It was widely believed that genetic approaches to understanding the clock were intractable and that clocks evolved independently in different organisms (Pittendrigh 1993). Thus, it was thought that studying the clock in fungi or other microbes would not reveal the mechanism used by the mammalian clock. In spite of this research climate, Jay persevered in studying the Neurospora clock and in the end proved the relevance of this system to mammalian chronobiology.

As Jay has pointed out, he happened upon daily (circadian) rhythms by chance after applying to Harvard's graduate program "on a whim" (Dunlap 2008). He was accepted and studied with J. W. (Woody) Hastings. He focused on bioluminescence in the marine organism Gonyaulax and determined the structure of luciferin (Dunlap and Hastings 1981a). The observation that Gonyaulax produces luciferin only during the night, when the light produced can be seen, made biological sense and launched Jay on the path to investigating the circadian clock that regulates daily rhythms in bioluminescence (Dunlap and Hastings 1981b; Hastings et al. 1981). He quickly realized that understanding the biochemical mechanism of the clock would also require a genetics approach, and this insight ledhimto the genetically tractable organismNeurospora, for which circadian clock regulation of development had been well established (Pittendrigh et al. 1959; Sargent and Briggs 1967). Jay moved to the University of California at Santa Cruz and joined Jerry Feldman's group. Feldman was the leading Neurospora geneticist studying the biological clock. He and his colleagues had isolated mutant strains with altered circadian periods in the developmental rhythm (Feldman and Hoyle 1973). Jay's arrival coincided with the newly emerging recombinant DNA techniques being developed for Neurospora (Case et al. 1979; Kinnaird and Fincham 1983; Schechtman and Yanofsky 1983). It was his goal to learnthe tools ofmolecular andNeurospora biology,with the hopes of cloning the clock genes. Jay ultimately succeeded in cloning a clock gene after taking a position as an assistant professor of biochemistry at Dartmouth Medical School. His group cloned the frq gene using a chromosome walk and showed that the cloned DNA complemented the arrhythmic phenotype of a frqmutant allele (McClung et al. 1989).

During his time at Dartmouth Medical School, Jay has opened up the field of circadian molecular biology and biochemistry and developed the tools and intellectual framework for approaching mechanistic questions that relate to three key observations of the clock: (1) the ability of the clock to free-run with a period of about a day in constant conditions; (2) the phenomenon of clock resetting by environmental cues; and (3) the capacity for the clock to run with a similar period when the organism is placed in different temperatures, a property called temperature compensation. His work has provided answers to each of these questions and led to an often-cited molecular model for this microbial FRQ-based circadian oscillator that has formed much of the basis for our understanding of the mammalian clock (Dunlap 1999).

As mentioned above, Jay was a pioneer in cloning clock genes. He conceived the criteria for identifying clock components and was the first to use experimental tests to establish the identity of a clock protein (FRQ) (Aronson et al. 1994). Jay was also the first to determine the biochemical activities of the clock molecules WC-1 and WC-2 and to show that these heterodimeric transcription factors are central to circadian feedback loops that, along with FRQ, form a circadian oscillator (Crosthwaite et al. …