NIH VideoCast - Clock Genes and Clock Cells: A New View

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Clock Genes and Clock Cells: A New View

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Air date:	Wednesday, May 12, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 277 * This only includes stats from October 2011 and forward.
Category:	WALS - Wednesday Afternoon Lectures
Runtime:	01:06:50
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	The molecular mechanism of circadian clocks has been uncovered by the use of phenotype-driven (forward) genetic analysis in a number of model systems. In mammals, circadian oscillations are generated by a set of genes forming a transcriptional autoregulatory feedback loop: these include: Clock, Bmal1, Per1, Per2, Cry1, Cry2 and Casein kinase 1 epsilon. Another dozen candidate genes have been identified and play additional roles in the circadian gene network such as the feedback loop involving Rev-erba. Despite this remarkable progress, it is clear that a significant number of genes that regulate circadian rhythms in mammals remain to be discovered and identified. As part of a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis screen using a wide range of nervous system and behavioral phenotypes, we have identified new circadian mutants in mice. These include new alleles of known circadian genes as well as novel circadian loci such, Fbxl3, an orphan member of the F-box protein family, which we have found to interact selectively with the CRY proteins to target them for degradation through the proteasome pathway. The discovery of ‘clock genes’ also led to the realization that the capacity for circadian gene expression is widespread throughout the body. Using circadian gene reporter methods, one can demonstrate that most peripheral organs and tissues can express circadian oscillations in isolation, yet still receive and may require input from the dominant circadian pacemaker in the suprachiasmatic nucleus (SCN) in vivo. We have used tissue-specific, conditional gene expression methods to analyze the relative contributions of central and peripheral circadian oscillators to circadian organization. The cellular autonomy of circadian clocks has raised a number of questions concerning synchronization and coherence of rhythms at the cellular level as well as circadian organization at the systems level. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.

NLM Title:	Clock genes and clock cells : a new view / Joseph Takahashi.
Author:	Takahashi, Joseph S. National Institutes of Health (U.S.)
Publisher:
Abstract:	(CIT): The molecular mechanism of circadian clocks has been uncovered by the use of phenotype-driven (forward) genetic analysis in a number of model systems. In mammals, circadian oscillations are generated by a set of genes forming a transcriptional autoregulatory feedback loop: these include: Clock, Bmal1, Per1, Per2, Cry1, Cry2 and Casein kinase 1 epsilon. Another dozen candidate genes have been identified and play additional roles in the circadian gene network such as the feedback loop involving Rev-erba. Despite this remarkable progress, it is clear that a significant number of genes that regulate circadian rhythms in mammals remain to be discovered and identified. As part of a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis screen using a wide range of nervous system and behavioral phenotypes, we have identified new circadian mutants in mice. These include new alleles of known circadian genes as well as novel circadian loci such, Fbxl3, an orphan member of the F-box protein family, which we have found to interact selectively with the CRY proteins to target them for degradation through the proteasome pathway. The discovery of "clock genes" also led to the realization that the capacity for circadian gene expression is widespread throughout the body. Using circadian gene reporter methods, one can demonstrate that most peripheral organs and tissues can express circadian oscillations in isolation, yet still receive and may require input from the dominant circadian pacemaker in the suprachiasmatic nucleus (SCN) in vivo. We have used tissue-specific, conditional gene expression methods to analyze the relative contributions of central and peripheral circadian oscillators to circadian organization. The cellular autonomy of circadian clocks has raised a number of questions concerning synchronization and coherence of rhythms at the cellular level as well as circadian organization at the systems level.
Subjects:	Biological Clocks--genetics Circadian Rhythm--genetics Mammals--genetics
Publication Types:	Lecture Webcast
NLM Classification:	QT 167
NLM ID:	101532594
CIT Live ID:	8250
Permanent link:	https://videocast.nih.gov/watch=8250

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