How genes control animal behavior is the big question my lab is interested in. We mainly study circadian (~24hr) rhythms of behavior, arguably the best understood behavior at molecular and cellular levels. We use the fruitfly Drosophila as a powerful model system that has led the way in circadian rhythm research and is ideal for analyzing behavior at the level of single genes, single neurons, neuronal networks and whole animal behavior. We use Genetics, Genomics & BioInformatics, Microscopy and Behavioral assays to build a holistic model of how flies anticipate daily environmental changes.
Adult flies have 24hr rhythms in their activity: they are more active by day, especially at dusk and dawn, and rest by night – paralleling human sleep/wake cycles. These rhythms persist in constant darkness, indicating that flies have an internal sense of time. Forward genetics helped identify a set of core clock genes that are essential for 24hr rhythms in constant darkness, and these genes work together in transcription / translation feedback loops, forming "molecular clocks".
A recent technical breakthrough we made has allowed us to obtain whole genome expression profiles from the master pacemaker neurons (LNvs) at different times of day. These datasets are helping us understand the biology of these neurons by giving us insights into how LNvs control the timing of their output signals, novel signaling pathways involved in circadian rhythms and a system-level understanding of how LNv gene expression is altered in different electrical states.
The larval clock neurons form a “minimal” circadian neural network with many fewer neurons than adult flies. We have been using this simplified circadian system to understand how clock neurons communicate to keep their molecular clocks synchronized with each other and to generate rhythmic behavior. The expectation is that what we learn in Drosophila will hold true for mammalian pacemaker neurons. Other projects ongoing in the lab include developing a novel decision-making paradigm in Drosophila.