From the 2000 Holiday Lectures — Clockwork Genes: Discoveries in Biological Time

More About Biological Clocks: Fly Circadian Activity

The fruit fly Drosophila melanogaster has been an essential experimental model for both early genetic studies of circadian rhythms and more recent examinations of molecular mechanisms. Researchers have devised methods to record daily activity fluctuations in individual flies. This animation series shows four experiments that compare the activity patterns of a wild-type fly keeping a normal schedule with those of a mutant fly apparently following a 19-hour internal clock. Furthermore, the role of light and dark in "re-setting" the biological clock of these two types of flies is also demonstrated.

This animation is based on the research of HHMI investigator Michael Rosbash, Ph.D.

Experiment 1: Wild-type flies are most active at dusk and dawn.

A single fruit fly is placed into a small glass tube. This tube is put into a device that has an infrared beam (invisible to the fly) aimed across the tube. Any motion of the fly that interrupts the beam registers as activity.

This activity is then plotted on an "actogram," which shows the amount of activity over the course of a 24-hour cycle. In an actogram, the 12 hours of light are represented by the light-colored bar at the top of the graph, and the 12 hours of dark by the dark-colored segment of the bar. Light and dark are controlled artificially and are represented in these animations by the turning on and off of the light bulb.

The first animation illustrates how a wild-type fly responds to a regular light-dark (LD) cycle. Its first bout of activity is at "dawn," just before and just after the light turns on. Its second bout of activity is at "dusk," again at the transition from light to dark. This second bout of activity lasts for a longer time, and its amplitude is greater than that of the morning activity bout.

For this animation, 24 hours of activity have been compressed into 5 seconds, with a total of four days being measured. In addition, although an actual fly does move somewhat during its quiet periods, the animation represents the fly as being motionless to make it easier to discern the difference between quiet and active periods.

Experiment 2: Flies in constant dark conditions have a slightly lengthened period.

In this experiment, the fly is kept in constant dark conditions (DD). This is also referred to as a "free-running" condition; the fly has no environmental cues to tell it where it is in its 24-hour cycle.

Under these conditions, a wild-type fly maintains both activity bouts, although the amplitude of the morning bout is greatly reduced. The other notable difference in a free-running wild-type fly is that its activity cycle is close to, but not exactly, 24 hours. The period is approximately 24.6 hours, so its activity bouts shift gradually later and later over successive days. This can be seen on the actogram by the activity bouts gradually shifting to the right.

Experiment 3: perS mutants have a shorter period of activity in constant dark conditions.

The perS mutant, under free-running DD conditions, exhibits a shortened period in its daily activity, which can be shown by looking at an actogram of a perS mutant over a series of days. Its free-running behavior has a shortened period between its two activity bouts. Since its cycle is only 19 hours rather than 24, the activity bouts shift to the left with each successive day.

Experiment 4: perS mutants are entrainable in light-dark conditions but maintain a shortened activity cycle.

Placing the perS mutant back into light-dark conditions returns the fly's morning activity bout to full amplitude and brings back a regular 24-hour cycle to its activities. However, the mutant fly's evening bout is advanced in time, occurring before the light-dark switchover. This shows that the mutant fly's circadian rhythms, although different from wild-type flies, are still present and can be "entrained" to respond directly to light stimulus from the environment.

Fly Circadian Activity Background

Living organisms have evolved internal timekeeping mechanisms to synchronize behavior and physiology with the cycles of day and night. These biological clocks have been found in organisms as diverse as fungi, fruit flies, hamsters, and humans.

This animation shows a real-time schematic demonstration of how circadian rhythms researchers record the daily activity of fruit flies. The activity charts, or "actograms," of a normal fly are compared with those of a fly that has a mutant gene important in maintaining a 24-hour period. Thus, the behavior, or phenotype, of a fly can be correlated with mutations at the level of the gene.

This animation was designed in conjunction with HHMI's 2000 Holiday Lectures on Science, Clockwork Genes: Discoveries in Biological Time (www.holidaylectures.org).

Fly Circadian ActivityTeaching Tips

The animations in this section have a wide variety of classroom applications. Use the tips below to get started but look for more specific teaching tips in the near future. Please tell us how you are using the animations in your classroom by sending e-mail to biointeractive@hhmi.org.

1. Use the animations to make abstract scientific ideas visible and concrete.

2. Explain important scientific principles through the animations. For example, the biological clocks animations can be used to demonstrate the fundamentals of transcription and translation.

3. Make sure that students learn the material by repeating sections of the animations as often as you think necessary to reinforce underlying scientific principles. You can start, restart, and play back sections of the animations.

4. Urge students to use the animations in accordance with their own learning styles. Students who are more visually oriented can watch the animations first and read the text later, while others might prefer to read the explanations first and then view the graphics.

5. Incorporate the animations into Web-based learning modules that you create to supplement your classroom curricula.

6. Encourage students to incorporate the animations into their own Web-based projects.

Fly Circadian Activity Credits

Director: Dennis Liu, Ph.D.

Scientific Direction: Michael Rosbash, Ph.D.

Scientific Content: Donna Messersmith, Ph.D.

Animator: Chris Vargas