Grant: Discovery Grants Program - Individual

Circadian clocks drive 24-hour rhythms in living things at all levels of organization, from single cells to whole organisms. In spite of the importance of clocks for daily cycles of sleep/wake in humans, seasonal flowering in plants, navigational ability in migrating butterflies, and countless other processes, we still don't know exactly how these clocks work at the molecular level. In eukaryotes, a set of “clock proteins” turns on and off specific genes in a 24-hour feedback loop. This “clock gene feedback loop” has been the dominant idea about how clocks work for many years. However, some rhythms can still be seen when these feedback loops are not functioning. My lab is trying to find out how clocks without the known feedback loops work, and we are in the forefront of the effort to expose the deficiencies in the old idea and find new clock mechanisms. We use the fungus Neurospora crassa because this organism is easy to grow, it has been studied for many years, and its rhythm of spore formation is easy to see. We have discovered genes that are important for maintaining rhythms without the known feedback loop. We have recently discovered the identities of the proteins made by two of these genes, and we want to find out how those proteins function in circadian time-keeping. One protein, VTOR1, helps cells adjust their growth rate to adapt to varying availability of nutrients. The other protein, PRD-1, is in a family that regulates gene expression, but we don't yet know its precise function in N. crassa. We know that PRD-1 is necessary for normal growth responses to nutrients, and the protein changes its intracellular location depending on nutrition, so both VTOR1 and PRD-1 are somehow linked to metabolism. Other labs have found that clocks in animals regulate nutritional responses, and clocks can also be regulated by nutritional states. Because we have already identified two genes involved in interactions between the clock and nutrition, our lab is very well-placed to use this model system to advance our understanding. We expect that this research will tell us more about how daily clocks are constructed in all organisms, and how living things can tell time. This will be useful to anyone studying how cells organize their internal processes, and anyone studying how organisms interact with the daily environmental cycles. Because circadian clocks are very important in human health, this research may also contribute directly to human welfare.