Grant: Discovery Grants Program - Accelerator Supplements

My research is aimed at answering this question: How do living things tell time? All living things bigger than bacteria, and even some bacteria, have internal clocks that drive daily rhythms in many biological processes. These "circadian" rhythms (circa diem = about a day) are important in human health: humans have circadian rhythms in activity, sleeping and waking, hormones, body temperature, etc. The internal clocks that drive these rhythms are found in individual cells of all higher organisms and in nearly every cell in the human body. When we suffer from jet lag, or work night shifts, we experience the negative effects of getting our cellular clocks out-of-synch with each other.     Because the internal clock can be found in individual cells, we can use simple organisms to study it. We are using the fungus Neurospora crassa, a common bread mould, as a model organism to study the mechanism of the clock at the molecular and biochemical level. This fungus is easy to grow in the laboratory, and has been studied for more than 60 years, so we know a great deal about its biochemistry and genetics. We use mutant strains that have disrupted clocks, and we are studying the biochemistry of these mutant strains to try to determine why their clocks are disrupted. Other labs have identified a small number of genes that are important in the normal clock mechanism, but we have found that the fungus can still be rhythmic even when these genes are defective. We are using a mutant that has an abnormality in the synthesis of lipids, the fatty molecules that make the membranes around cells. When the level of a particular lipid, diacylglycerol, is high in the mutant, the fungus is rhythmic with a slow clock, even when other well-known clock genes are mutated. Diacylglycerol in known to be an important signalling molecule in animal cells, activating enzymes that control many cellular processes. We are looking at the effects of diacylglycerol on the signalling enzymes in Neurospora to try to understand how it affects the clock. This research may help us identify new components of the clockworks, and this can help us understand how the fungus, and possibly other organisms, use their biochemistry to tell time.