| How Biological Clocks Work

 Anyone who has traveled has experienced jet lag-that groggy realization that   while your day is beginning in Washington, DC, the night you just left in San   Francisco is hardly over. Jet lag is an inconvenient reminder that the body   is set to a 24-hour clock, known by scientists as circadian rhythms, from the   Latin *circa dies*, "about one day." An internal biological clock is fundamental   to all living organisms, influencing hormones that play a role in sleep and   wakefulness, metabolic rate, and body temperature. 
 Disruption of circadian rhythms is involved in changes in sleep patterns and   can exacerbate the course of serious mood disorders, such as bipolar disorder   and depression. Other types of illnesses also are affected by circadian rhythms;   for example, heart attacks occur more frequently in the morning while asthma   attacks occur more often at night. 
 Although biological clocks have been the focus of intensive research over   the past four decades, only recently have the tools needed to examine the molecular   basis of circadian rhythm become available. Early studies pointed to an area   of the brain, the hypothalamus, as the location of the circadian pacemaker in   mammals. More recent findings show proteins called cryptochromes, located throughout   the body, are also involved in detecting changes in light and setting the body's   among different inbred strains of rodents. 
Genes that code for the clock protein, PER, glow in the head and   other body parts of a fruit fly. Researchers made the clocks glow by engineering   transgenic strains of flies in which the same genes that illuminate a jellyfish   and a firefly's tail are attached to PER. The gene for luciferase,the enzyme   that glows intermittently in fireflies, was expressed along with period to reveal   when the clock protein was being produced. Flies were also molecularly altered   to brightly mark the clock sites with Green Fluorescent Protein, which glows   constantly in jellyfish. *Source: Jeffrey Plautz, Ph.D., Stanford University;   Steve Kay, Ph.D., Scripps Research Institute*
 In 1971, the first circadian gene was discovered in the fruit fly; a second   circadian gene was detected 13 years later. Following these discoveries, however,   the search for clock genes in other organisms faltered. Not until 1997 was the   first circadian gene found in a mammalian model, the mouse. This discovery immediately   accelerated the search for other clock genes, and findings in higher order animals   are yielding a consistent picture of the role and function of circadian rhythms   in organisms from blue-green algae to plants to mammals. 
 Today, we know the most about the workings of the biological clock in the   fruit fly and a peek inside its mechanisms illustrates the complex elegance   of the rhythms of life. The fly's clock consists of a core system of four regulatory   proteins that interact to give the clock periodicity. The cycle begins when   two of these proteins, CLOCK and CYCLE, bind together and increase the production   of two other proteins, PER and TIM, the levels of which slowly accumulate over   time. When enough PER and TIM are made, they inactivate the CLOCK-CYCLE complex,   slowing their own production and signaling the end of the cycle. |
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