Patricia L Lakin-Thomas
Associate Professor, Department of Biology
PhD, UC San Diego
Lay Research Summary
In my lab, we are interested in circadian rhythms, the daily biological clocks that give you jet lag when you fly across time zones, and that cause health problems for shift workers. Almost all living organisms have biological clocks, and they seem to work in similar ways in different organisms. T ...read morehese clocks keep time even when the organism is isolated from the outside world, and even single cells isolated in a Petri dish can keep time. We work with a fungus, a bread mold called Neurospora crassa, that makes spores at the same time every day. It's easy to grow it and to genetically engineer it, so it's a great model organism for studying clocks. We look for genes that are involved in building the clock mechanism. We recently found two genes that mess up timekeeping when those genes are mutated. One of those genes is important in controlling how other genes are turned on and off. The second gene is important in sensing nutrients and controlling the growth of the fungus. This helps make a connection between nutrition and timekeeping, and might help explain why shift workers and other people with chronically out-of-sync body clocks may have problems with obesity and diabetes. Am I looking for a cure for jet lag or a treatment to help shift workers? Not really- I just want to know how a fungus can tell time! read less
Scientific Research Summary
My research is aimed at answering this question: How do living things tell time? I am interested in circadian rhythms, the daily activity cycles driven by internal clocks in all eukaryotes and some prokaryotes. The goal of my research is to describe the mechanism of a circadian clock at the ...read moremolecular and biochemical level. Because circadian rhythmicity is a fundamental property of all eukaryotic cells, an understanding of the mechanism of rhythmicity will give us important insights into how cells function. I work with the filamentous fungus Neurospora crassa, a model organism that is at the forefront of circadian rhythm research. We use the rhythm of spore-formation (conidiation) as a visible marker for the state of the internal clock. Previous research has shown that the FRQ, WC-1 and WC-2 proteins are important for rhythmicity in Neurospora, but recent work has shown that conidiation rhythms can continue in their absence. I am interested in finding the oscillator that drives rhythmicity in the absence of FRQ (the FRQ-less oscillator, or FLO). I have found that a mutation in lipid metabolism, chol-1, reveals rhythmicity in FRQ-less strains growing in constant conditions. I have also demonstrated that cycles of heat pulses reveal the existence of the FLO in FRQ-less strains without the chol-1 mutation. We are using these conditions as tools to visualize FRQ-less rhythms and assay the functioning of the FRQ-less oscillator. Our current goal is to identify the components of the FLO, determine how they interact to produce an oscillator mechanism, and determine how that oscillator interacts with the FRQ/WCC oscillator. My lab’s strategy is to search for genes that affect the FLO, by using standard genetics to introduce known clock mutations into FRQ-less strains, and by mutagenesis to create new mutations affecting FLO. We have identified several mutations that disrupt FLO and we are characterizing these new FLO-affecting genes. We have mapped and identified two of these genes, and we are now carrying out functional analyses to determine where and when the products of these genes are expressed, and what proteins they interact with. We are also looking at the effects of our FLO-affecting mutations on the expression of clock-controlled genes and biochemical rhythms, and on the function of the FRQ/WC oscillator. read less
A component of the TOR (Target of Rapamycin) nutrient-sensing pathway is essential for circadian rhythmicity in Neurospora crassa.
PRD-1, a component of the circadian system of Neurospora crassa, is a member of the DEAD-box RNA helicase family.
Journal: J. Biol. Rhythms
The genetics of circadian rhythms in Neurospora.
Journal: Advances in Genetics
A new mutation affecting FRQ-less rhythms in the circadian system of Neurospora crassa.
Journal: PLoS Genet
Transcriptional feedback oscillators: Maybe, maybe not.
Journal: J. Biol. Rhythms
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