The liver, on the other hand, is more slothlike. It is less attentive to the master clock, and it takes several days for the liver to catch up with changes in the master clock. Incidentally, the problems related to jet lag and night shift work are often caused by the liver's inability to respond rapidly to changes in the sleep-wake cycle.
One key to understanding the intricacies of the mammalian clock and to addressing problems with jet lag and certain sleep disorders is discovering the different genes that communicate the timing of the master clock with the circadian rhythms of the various tissues. Not all of these genes are known.
Identifying the Clock Genes
Panda and Sato performed gene array experiments on different samples of mammalian tissue to determine which genes are cycling and which might be components of the clock.
These experiments involve taking cells from the particular tissues, recovering the cells' expressed genes (in the form of messenger RNA, or mRNA), chopping the mRNA into fragments, and plopping the mixture of fragmented mRNA on a gene chip -- a glass or silicon wafer that has thousands of short pieces of RNA attached to it with sequences corresponding to known genes.
These short pieces are laid out in a grid, and genes that are expressed in the tissue will bind to complementary pieces of mRNA on the grid. Then by looking to see which pieces on the grid have RNA bound to them, the scientists are able to determine which genes were being expressed in the sample.
DNA and RNA chips have become a standard tool for genomics research in the last couple of years, and scientists can quite easily put a large number of different oligonucleotide pieces -- conceivably even all the known genes in an organism -- on a single chip.
The Scripps Research and GNF team charted the time course of circadian rhythms by looking at the expression of
Contact: Keith McKeown
Scripps Research Institute