We currently have two research focuses in the lab: circadian clock and RNA interference (RNAi).
CIRCADIAN CLOCK Circadian clocks have been described in almost all organisms ranging in complexity from single cells to mammals and function to control daily rhythms in a variety of biochemical, cellular, physiological and behavioral events. These rhythms have a period close to 24 hours (circadian) and persist in the absence of external time cues. One of the most important characteristics of circadian rhythms is that they can be synchronized or entrained by environmental signals, the strongest of which are light and temperature. In humans and mammals, circadian clocks control events such as sleep-wake and activity cycles, body temperature cycles, endocrine functions, and gene expression. Clinical consequences in humans including sleep disorders and depression can be observed when the clock malfunctions. The influence of a functional clock on temporal regulation is evident from the decreased performance of shift workers and the jet lag felt by long distance travelers.
Our lab is using filamentous fungus Neurospora crassa, one of the best studied model organisms for circadian clocks, to understand the molecular mechanisms of the circadian clock. In Neurospora, the circadian clock acts to control a variety of processes, and previous studies have shown that the Neurospora circadian clock is an auto-regulated negative feedback loop in which the frequency (frq) gene is an essential component.My laboratory is using molecular, biochemical, and genetic approaches to answer three general questions: 1) What are the components of the input pathways to the clock and how do environmental signals entrain the clock; 2) What are the genes that make up the oscillator and how are they regulated to generate rhythms and 3) How does the clock control rhythmic output events? In the long term, these studies will enable us to compare clock mechanisms of fungi with those of other eukaryotes and to help guide research in other organisms.
RNA INTERFERENCE The production of double-stranded RNA (dsRNA) is known to elicit RNA interference (RNAi) in most eukaryotes and interferon response in mammals. RNAi and related pathways are evolutionarily conserved gene silencing mechanisms that regulate gene expression, development, genome stability, and host-defense responses. The filamentous fungus Neurospora crassa, an organism that broadly employs gene silencing in regulation of gene expression, offers a unique and powerful system for understanding the RNAi pathway and its function in eukaryotes. Using Neurospora as a model system, we have revealed the mechanism of the RISC activation process in the RNAi pathway. We also showed that dsRNA activates a novel signaling pathway to induce transcription of many genes in Neurospora, including most of the RNAi components, putative antiviral genes, and homologs of the interferon stimulated genes; this activation is analogous to the interferon response in mammals. Our current research is focusing on the understanding of the regulation of RNAi components and on the involvement of RNAi pathway in various cellular processes.
RESEARCH INTERESTS
Molecular mechanisms of circadian (daily) biological clocks
Mechanisms of RNA interference and gene silencing
RECENT PUBLICATIONS
Huang G, Chen S, Li S, Cha J, Long C, Li L, He Q, Liu Y., "Protein kinase A and casein kinases mediate sequential phosphorylation events in the circadian negative feedback loop." Genes & Development, 21(24):3283-95, 2007
Maiti, M., Lee, HC., and Liu, Y., "QIP, a putative exonuclease, interacts with the Neurospora Argonaute protein and facilitates conversion of duplex siRNA into single strands" Genes & Development, 21(5):590-600, 2007
Choudhary S, Lee HC, Maiti M, He Q, Cheng P, Liu Q, Liu Y., "A double-stranded-RNA response program important for RNA interference efficiency." Mol Cell Biol., 27 (11):3995-4005., 2007
He Q, Cha J, He Q, Lee HC, Yang Y, Liu Y, "CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR complex to close the Neurospora circadian negative feedback loop." Genes & Development, 20(18):2552-65, September 2006
Cheng, P., Q. He, Q. He, L. Wang, and Y. Liu., "Regulation of the Neurospora circadian clock by an RNA helicase" Genes & Development, 19:234-241, 2005
SIGNIFICANT PUBLICATIONS
He Q, Liu Y., "Molecular mechanism of light responses in Neurospora: from light-induced transcription to photoadaptation." Genes & Development, 19(23):2888-99, 2005
He Q, Cheng P, He Q, Liu Y., "The COP9 signalosome regulates the Neurospora circadian clock by controlling the stability of the SCFFWD-1 complex." Genes & Development, 19(13):1518-31, 2005
Yang, Y., Q. He, P. Cheng, P. Wrage, O. Yarden, and Y. Liu., "Distinct roles for PP1 and PP2A in the Neurospora circadian clock." Genes & Development, 18:255-260, 2004
He, Q.*, P. Cheng*, Y. Yang, L. Wang, K. H. Gardner, and Y. Liu, "White Collar-1, a DNA-binding transcription factor and a light sensor" Science (cover article), 297:840-843, January 2002
Yang, Y., P. Cheng, and Y. Liu., "Regulation of the Neurospora circadian clock by casein kinase II" Genes & Development, 15:994-1006, June 2002
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