Paul Taghert Research Abstract
My laboratory seeks to understand the organization, regulation and outputs of circadian neural circuits in the Drosophila brain. We take advantage of the remarkable molecular genetic methods that are available with this model system. Our principal contributions include (i) identifying roles played by the PDF neuropeptide and its receptor: We have analyzed its role genetically, demonstrated it to be a synchronizer of the molecular clock in individual pacemaker neurons under constant conditions. More recently, in collaboration Tim Holy’s lab, (ii) we have employed novel imaging techniques to perform brain-wide scanning in real-time in vivo across the entire day (Liang et al., 2016 Science): Each pacemaker group has its own specific phase of activity (in contrast to the phases of their clocks, which are synchronous). Unexpectedly, PDF signaling is critical to delay Evening Oscillator activity ~8 hr following the dawn, and so generate its distinct Evening Oscillator activity phase. We are currently expanding the scope of our imaging studies to determine in vivo realtime 24 patterns of changes in voltage and cyclic nucleotides in this pacemaker network. In addition, we have found that PDF sensitivity cycles across the day (Klose et al., 2016 Neuron) – with greatest sensitivity around dawn – and have shown this cycle critically defines the time of neuropeptide modulation. Many of our current studies use genetics, imaging, and biochemistry to pursue the molecular basis for signaling downstream of the PDF receptor.