When Dartmouth’s C. Robertson McClung heard that the Nobel Prize in physiology or medicine had been given for work done in his own research field – the genetic underpinnings of the daily life cycles known as circadian rhythms – he swears his reaction was not, as mine would have been, “Darn; why didn’t I win?”
“I thought these guys were richly deserving. I’ve been thinking for the last 10 or 15 or 20 years that their stuff is good enough – when is it going to happen?” said McClung, a biology professor, concerning the prize, which was announced Monday.
However, he agreed that he and colleagues will get an indirect boost from the prize for three U.S. researchers, the first to link specific genes to changes in circadian rhythms.
“(The Nobel Prize) is a merit badge for the whole field, a validation that is important to study,” he said. “It’s validation both in scientific circles and lay circles. At cocktail parties, if somebody asks you what you do, it’ll come up.”
The Nobel Prize was given Monday to three American academics – Jeffrey Hall, Michael Rosbash and Michael Young – because of their discovery of how a so-called “period gene” caused proteins to be created in daily rhythms that trigger changes in fruit flies, the workhorse insect for much genetic and biology research.
McClung compares the genetic mechanism to a thermostat that turns your home heater on when the indoor temperature falls, then turns it off when the temperature rises, creating a negative feedback loop.
Similarly, he said, “The period gene turns on, accumulates (proteins), then it feeds back to turn itself off – that’s how you get a 24-hour rhythm.”
“Flies, fungus, mice and people all have a common architecture of a negative feedback loop,” he added – indicating not only that this appeared very early in evolution but that it is a useful mechanism worth knowing more about.
McClung said all three of the new Nobel laureates have continued doing good work in the field since their initial breakthrough.
“They were not one-trick ponies that did one really cool thing,” he said. “They did really cool things over and over.”
Circadian rhythms have been subject of interest since at least the ancient Greeks, and many of us know about them from suffering through jet lag or working the night shift. But the ability to detect and react to changes in daylight is part of virtually all living things, and is important in lots of not-very-obvious ways.
“With photosynthesis, plants feed in daytime and don’t eat a night, so there’s an obvious need for temporal coordination with the day-night cycle,” McClung said.
That coordination is necessary for more than day-to-day activities, he added. “Different plants flower seasonally – but how does the plant know what season it is? Basically, plants measure day length, or really night length, and react. “In order to determine that, you’ve got to have a good 24-hour clock.”
It’s October, so that made me think of leaf-peeping, which I’ve been told kicks off each year because of changes in daylight patterns. McClung agreed that this sounded reasonable but gave a suitably cautious researcher response: “I don’t know that has been substantiated scientifically.”
McClung dived into circadian rhythms when he came to Dartmouth as a postdoc in 1986, working with Professor Jay Dunlap’s group on fungus, and he’s still at it. This summer, he was co-author on a paper that linked genes in a relative of the mustard plant with the way that stress from drought made it shut down leaf pores at night to preserve moisture.
This could lead to ways to breed or genetically modify crops so they adapt better to our climate-changed world.
It also connects with other research that shows a non-obvious (non-obvious to me, anyway) link between stresses and circadian rhythms. Many living things have evolved to react to stresses linked to daily patterns, such as being eaten by predators that come out at night, or suffer from diseases triggered by seasonal temperatures.
“The clock is involved in the ability of plants to respond to stresses – biotic ones, like pathogens or herbivores, or abiotic ones like drought or cold shock,” he said. “Responses tend to be maximal at a specific time of day, the time they typically encounter that stress.”
The research linked, for the first time, these genetic changes with physiological changes. That is scientifically interesting, but if it can be used to help grow more food in a stress-filled world, then it’s even better.
“I think this is a great example of how basic science can – with a lag – be turned into betterment of mankind,” McClung said.