On Oct. 2, 2017, The Nobel Assembly at the Karolinska Institute announced that Michael Rosbash, a Howard Hughes Medical Institute (HHMI) investigator at Brandeis University, Jeffrey C. Hallexternal link, opens in a new tab of Brandeis University and Michael W. Youngexternal of the Rockefeller University are the recipients of the 2017 Nobel Prize in Physiology or Medicineexternal for their discoveries of molecular mechanisms controlling the circadian rhythm.

Rosbash, who became an HHMI investigator at Brandeis University in 1989, Hall, and Young were highlighted for discoveries that have revealed the genetic underpinnings of the circadian clock. Circadian clocks are active throughout the body’s cells, where they use a common genetic mechanism to control the rhythmic activities of various tissues.

Using fruit flies as a model organism, this year’s Nobel laureates isolated a gene that controls the normal daily biological rhythm. They showed that this gene encodes a protein that accumulates in the cell during the night, and is then degraded during the day. Subsequently, they identified additional protein components of this machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell. We now recognize that biological clocks function by the same principles in cells of other multicellular organisms, including humans.

In 1984, Rosbash and Hall cloned the period gene. Several years later, they proposed a mechanism by which a molecular 24-hour clock might work — a transcriptional negative-feedback loop. Their model still holds up, despite discoveries of additional circadian rhythm genes, and it applies to humans as well as fruit flies. In essence, the genes that are part of this loop activate the production of key proteins until a critical activity of each accumulates and turns off transcription. Phosphorylation as well as light regulation of these key proteins is also important to the timing mechanism. Although many details remain to be worked out, “there is an emerging picture of feedback mechanisms that regulate the levels and activity of key circadian proteins, which ebb and flow in harmony with daily light and dark cycles,” Rosbash says.

Over the years, Rosbash and Hall identified other significant circadian genes and the function of their proteins, with the goal of understanding how the various pieces of the clock fit together. Rosbash’s group has also uncovered dual body clocks in the brain of fruit flies that independently govern bursts of morning and evening activity. The clock that initiates the morning activity, however, also helps to reset the second clock that regulates movement in the evening. Rosbash speculates that mammals possess similar dual circadian clocks. The integration of multiple clocks is probably important not only for maintaining a precise 24-hour cycle but also for adapting physiology to seasonal changes in day length, at least in animals.