Jay Dunlap

Major contributions by Jay Dunlap include his work investigating the role of frq and wc clock genes in circadian rhythmicity, and his leadership in coordinating the whole genome knockout collection for Neurospora.

He and his colleague Jennifer Loros have mentored numerous students and postdoctoral fellows, many of whom presently hold positions at various academic institutions.

[1][2] For his postdoctoral fellowship, Dunlap attended the University of California, Santa Cruz and started working with Jerry Feldman, who had successfully isolated clock gene mutants in Neurospora that have abnormally long or short circadian-oscillation periods.

[3] Dunlap learned basic molecular techniques as he worked alongside fellow biology graduate students in other labs.

Although clock gene mutations were also identified in Drosophila and Chlamydomonas,[1] Dunlap studied Neurospora in his postdoctoral work, as a wider array of biochemical and genetic tools were applicable to the species at the time.

During her graduate work, Jennifer Loros observed mutant frq9 as a recessive, arrhythmic, and phenotypically null allele at the frq gene.

[8] Her observation, combined with the ability to transform Neurospora with exogenous DNA, provided the basis for a novel strategy to clone frq, namely by transformation-based rescue of the null mutant behavioral phenotype.

Furthermore, the lab manually sequenced roughly 9kb and conducted transcript mapping on the frq genomic region; the results were published in Nature in 1989.

In 2009, Dunlap and colleagues showed that the FRQ protein is phosphorylated at over 100 sites in a highly reproducible and time-of-day-specific manner[12] and that casein kinase 2 establishes and maintains temperature compensation within the circadian clock.

Additionally, Dunlap and colleagues discovered that the daily phosphorylation of FRQ governs its ability to interact with the proteins in the negative element complex.

[2] These experiments eventually led to the universal recognition of entrainment via light-induced changes in a specific variable of the circadian oscillator, later observed in Drosophila and mammals.

Although it was established that heterodimeric WC-1/WC-2 transcription factor was required for light-induction of frq, researchers believed that WC-1 and WC-2 did not have a direct role in the process of photoreception.

[25] The search for CCGs finally culminating in the complete description of the circadian transcriptome of Neurospora where as much as 40% of the genome is controlled on a daily basis by the clock.

One part of the mechanism is that Gonyaulax produces luciferin and luciferase at night when the emitted light can be seen, while production of the substrate and protein decreases at dawn.

The realization that a complete understanding of this biochemical process would also require a combined genetics approach led Dunlap to begin his study of the circadian clock of the Neurospora.

Dunlap, along with Jennifer Loros, Arun Mehra, and Van Gooch, adapted firefly luciferase for expression in Neurospora, thereby greatly expanding the ability to analyze strains.

[28] The novel method used by Dunlap and his colleagues to characterize and use the luciferase gene improved expression by 3 log orders and allowed for the correction of several errors in the Neurospora literature.

[29] N. gardneri is found growing beneath palms in the Amazonian forest and the nocturnal bioluminescence is believed to be used by the fungus to attract insects at night as an aid to spore dispersal.

He spearheaded the push to knock out all 10,000 genes in the Neurospora genome and construction of a high-density single nucleotide polymorphism map.

Finally, Dunlap revolutionized the role of luciferase expression by examining codon bias and is using its implications in Neurospora and other organisms.

The circadian nature of cellular processes in humans may be leveraged to target cancerous cells more effectively and treat sleep abnormalities.

[33] This form of communication may prove to be an adaptive feature of biological clocks and enable beneficial responses to changes in environment.

Additionally, Dunlap works with William Cannon and Jennifer Hurley to develop mathematical models describing circadian clock function.

Dunlap has also been involved in work examining the hierarchical network of transcription factors that govern circadian output.