Jay C. Dunlap

An early interest in oceanography led me to marine organisms, one of which used a circadian clock to control daily cycles of bioluminescence. This biological clock interested me, and to describe its mechanism I became a geneticist, focusing on the simplest eukaryotic circadian system, that of the filamentous fungus Neurospora. We cloned clock genes, carried out screens to identify clock components and clock regulated genes, and studied their regulation. To test the conceptual models that naturally arose, we developed new tools allowing manipulation of clock protein levels, demonstrating that the circadian oscillator comprised a cell-autonomous time-delayed transcriptional negative feedback loop wherein clock genes encoded proteins that fed back to reduce clock gene transcription; the chief conduit of clock output was through transcriptional regulation of clock-controlled genes encoding products that don't impact the feedback loop. Rapid light-induced transcription of a clock gene, mediated by a novel light-activated transcription factor, underlies resetting, and specific post-translational modifications of clock proteins underlies both the long period of the rhythm and temperature compensation. More recently, our work has expanded to include mice and mammalian cells in culture, and also to developing tools for high throughput gene knockouts that we have used for whole genome functional genomics.