During the dog days of summer, millions of us migrate to the nearest watering hole or beachfront property to have our fun in the sun. We may not realize it when we are lounging by the pool or bouncing a beach ball around, but those seemingly mindless activities actually fulfill a primeval pattern connecting all living things to the sun. The pull of this celestial orb is emotional, spiritual, and physical—commanding the reverence of ancient Greeks and modern-day students alike. So why are we so drawn to light?
For us humans, sunshine triggers our brains to produce feel-good chemicals and helps us maintain a good biological rhythm. As days get shorter, the lack of sunlight brings on the winter doldrums or even full-blown depression, causing many people to sleep more, eat less, and withdraw socially.
But that connection with light is hardly unique to our species. In fact, few living creatures could function without light. The sun’s rays trigger profound changes deep beneath the surface of organisms as dissimilar as fungi, ferns, and fish. Special light sensors on the leaves of a plant or in the eyes of an animal capture sunlight and translate it into biochemical messages crucial to survival. These instructions can direct a plant to grow taller, tell a pathogen to evolve new properties, or help a baby start sleeping through the night.
The cause and the effect are clear, but scientists are beginning to uncover the many steps that lie in between. Their findings may not only help us understand light’s effects deep within our bodies, but also enable us to harness its power for our own purposes. At Duke, Meng Chen, Nicolas Buchler, and Debra Brandon are among dozens of researchers engaged in studies related to light. Though their subjects and methods are different, these three researchers are finding surprising ways that light matters to all kinds of living things.
It Isn't Easy Being Green
Of all living things, plants are undoubtedly the most susceptible to the whims of the sun. Unlike animals that can move if they find themselves in an environment that is too dark or too crowded, plants are stuck in one place.
“They don’t get to pick where their seed is going to land, so they have to use a different strategy,” says Meng Chen, an assistant professor of biology at Duke. “Plants monitor their environment and change their own physiology in order to adapt and maximize their ability to survive in a specific location.”
It is also their ability to adapt at a developmental level that sets plants apart. In animals, the blueprint of the body—where to put the tail, the arms, and legs—is all laid out in the darkened environs of the embryo. In plants, the real development doesn’t happen until they see the light of day. If they detect sunshine, they’ll start laying the groundwork to turn it into energy. If they emerge under the shade of a canopy, they’ll sprout a limb to seek out more light.
“Light controls everything—whether a plant needs to turn green, when to flower, how much to grow, when to grow,” says Chen, who has been studying the effects of light for the past ten years.
“...we may be able to use our work in plants to actually get at the basic principles of how cancer works in humans.”
As Chen explains it, plants use light in two different yet interconnected ways: as a source of energy and as a source of information. Light cues tell a plant when to germinate or when to grow, or they can direct the production of tiny structures known as chloroplasts that turn light into energy. This process of turning sunshine into fuel is photosynthesis, a term that may conjure memories of grade-school biology. Yet little still is known about how it works.
“We have no idea what is turning plants green,” says Chen. “We know it is the chloroplasts, but we don’t know how plants make chloroplasts—how that signal from light ultimately gets transmitted and translated within the organism to turn a plant green.”
When he was a postdoctoral fellow, Chen discovered a key character in this colorimetric cascade. He did so by treating plant seeds with a powerful chemical that introduces defects into their DNA and watching to see whether any of the resulting sprouts failed to respond to light and turn green. After looking at 24,000 seedlings, he finally found what he was looking for—a plant as white as milk. Chen then spent the next four years isolating the mutated gene, which he named Hemera after the Greek goddess of day.
Hemera specifically responds to the colors red and far-red, a segment of the visible spectrum that lies between red and infrared light. It is one of many such light-signaling molecules that plants use to capture all the colors of the rainbow. Because each color represents a different environmental reality, plants can use the information transmitted through these molecular entities to gauge and respond to the world around them, much like we would use the weather report to decide whether to grab an umbrella or a heavier coat. For example, when Hemera is turned on by red, the plant sees an open field with plenty of direct sunlight. When it is turned off by far-red, the plant sees shade, with all of the red light being soaked up by leaves overhead.
Having discovered one link through Hemera, Chen and his colleagues now are generating more blind plants to see whether they can piece together the entire chain of events connecting light to behavior. They’ve already found another gene that can make the albino Hemera mutant plant green again, essentially restoring sight to the blind. Chen named it Son of Hemera. Once scientists fully understand how plants respond to light, they may be able to harness the properties of photosynthesis to generate novel biofuels or alternative sources of energy. But Chen glimpses an even bigger goal on the horizon: solving the biological puzzle of cancer.
The unlikely jump from plant biology to human disease underscores the reality that plants and animals still have a lot in common, despite eons of evolutionary separation. Chen sees a possible similarity in the way they physically arrange their cell’s genetic programs or genomes. Molecules that manage a plant’s response to light seem to reside in special pockets within the cell, called photobodies. The human counterpart of these molecules, which evolved to respond to the cancer-causing damage from UV rays, sometimes resides in similar structures called nuclear bodies.
“It taps into what I think is the most important question in biology. At this point we have sequenced the genome of many organisms, but knowing the genes is only giving us maybe 10 percent of the story,” says Chen. “To get at the rest of it, we have to understand how the genome is physically arranged and how that arrangement impacts things like responding to light or turning into cancer. Therefore we may be able to use our work in plants to actually get at the basic principles of how cancer works in humans.”
In the end, these nuclear bodies could be serving as a meeting place where all of the incoming signals—cues such as light, temperature, or the presence of particular hormones—are integrated into a common message. Researchers already know, for example, that plants use light and other signals to measure the length of the night, which tells them whether it is spring or fall and, consequently, when they should produce flowers. Every day, they use this information to reset their internal clock, a circadian rhythm that calls all the cellular shots for twenty-four hours until the sun rises again.
Though the circadian clock was first observed in plants, researchers have since shown that animals, fungi, and some bacteria also have an internal timekeeping mechanism that coordinates their physiological processes. This free-running clock knows when to turn on “day genes,” messages in our DNA that when translated can raise our body temperature, get our blood pumping, and make us more alert. It also knows when to turn on “night genes,” which lower our blood pressure, suppress our digestive system, and dose us with hormones to help us sleep.
From an evolutionary standpoint, the circadian clock is as old as the hills. But if you go back a few billion years, you could probably find a time when the clock didn’t exist. Back then, the inner workings of our single-celled ancestors were completely dependent on external cues. If there weren’t a bright light shining down, the day genes wouldn’t come on, even if it was the middle of the day. Did that light-dependent lifestyle create a problem for organisms, and if so, is that why we evolved to carry a clock deep within our DNA?
That is the question that motivates Nicolas Buchler, an assistant professor of biology and physics who studies the evolution of the circadian clock. He and others in the clock field believe that organisms with a free-running clock have gained an internal representation of what’s going to happen in the external world. “So at four in the morning, your body could start getting ready for sunrise at six,” says Buchler. “That extra preparation could be enough to give you an advantage over someone who can only respond the moment the sun comes up.”
In other words, the early bird gets the worm.
Buchler cites a number of experiments that support this theory. In one such study, researchers genetically engineered cyanobacterium to have clocks that ran longer or shorter than the normal twenty-four-hour period. The bacteria with the screwed-up clocks didn’t grow as well, showing there was a cost for bad timing.
But it was another study—a computer simulation—that drew Buchler into the clock field. In the experiment, researchers modeled a virtual population of 100 cells that responded to light. They then mimicked natural selection, picking out the computer-created cells that responded to light in the right way—such as turning on their day genes at the right time—and then looked to see whether those cells had an advantage over the rest of the population. Initially, their results suggested that the evolved cells didn’t dominate the others. But the researchers soon realized the problem was that the simulation modeled a completely artificial source of light—akin to a fluorescent lamp controlled by an on/off timer. So they tweaked their system to include data gathered from a photometer placed in the middle of a forest. Suddenly, those free-running clocks—often called internal oscillators because they oscillate around the clock—emerged.
“They just left the paper at that, with no explanation for why having this natural sort of light was key to the evolution of these internal oscillators,” says Buchler. “But as a scientist, I just had to know what it was about noisy, variable light that played such a pivotal role.”
Unlike the light of Edison’s creation, natural light doesn’t turn on and off with the flick of a switch. Natural light is inconsistent—think stormy days and full-moon nights—and generates all kinds of mixed signals for a plant or animal trying to find a rhythm. Buchler’s hypothesis is that a circadian clock gives an organism an internal momentum, a type of inertia that filters out the noise to give a clear signal of day or night. A synthetic biologist by trade, he also is using computers to test his theory.
“The curse of being a synthetic biologist is you are dealing with an artificial system. There are a lot of things we don’t understand, so we have to do a lot of troubleshooting,” he says. “In contrast, if you are a geneticist, you have a system that is already working. Evolution has done all of the work for you.”
To model evolution on a computer, Buchler first has to build what he calls toy models, a simple circuit of two genes capable of oscillating around the clock. He then will add in a number of real physiologic and environmental parameters to determine which conditions are necessary for the circuit to start oscillating. For now, Buchler will be happy if he can get his toy models to oscillate every two hours, but eventually he hopes to have a working model of the full twenty-four-hour cycle of a circadian clock.
the early bird gets the worm.
Once he has perfected a toy circuit, his goal is to build it in yeast—a clock-less organism—to see whether he can use natural stimuli to recapitulate the evolution generated on the computer. Last year, Buchler won the NIH Director’s New Innovator Award to fund the project, which he titled “Rewiring the Yeast Brain: Redundancy and Interference in Gene Regulatory Networks.” In the proposal, he likened his toy circuits to a “brain” that could be transplanted into yeast to model how pathogens might evolve and rewire their gene networks to respond to attack from the host immune system or antibiotic treatment.
Buchler says that understanding the evolution of responses to environmental cues could have implications that go far beyond simple organisms. For example, he wonders if the advent of electricity—which allowed people to defy nature’s clock and create light at any time—could alter the circadian clock in a way that can’t be turned back. Studies have shown that medical-school residents who work back-to-back shifts with little exposure to the outside world are slower to react and more error-prone than in normal cycles. Similarly, people traveling overseas can feel out of sorts until they are exposed to enough day-night cycles to adjust their internal clock or, more often, return to their home time zone.
“Now that we have a bit of control over our clock, I imagine there could be benefits to using technology to reset our alarms, but there could be consequences, too,” he says. “It is an interesting evolutionary question to think about. Because the circadian clock is integrated into so many different processes—behavior, metabolism, physiology—altering it will undoubtedly have long-term effects.”
Into the LightThough light may be vital for setting our daily rhythms, humans spend their first nine months of development completely in the dark. When babies emerge into a world of light, it can take time for them to adjust. And in no case is that time more critical than with babies born prematurely. For many years, it was standard practice to care for infants in neonatal units in complete and total darkness. Keeping babies in the dark protected them from the sometimes negative effects of bright light—which could stress out babies whose blink responses had not yet matured—and mimicked the environment of the womb.
But researchers such as Debra Brandon, an associate professor of nursing at Duke, have argued this approach doesn’t exactly recapitulate life in the uterus, where exposure to the mother’s own circadian rhythms can set up a similar pattern for the baby. As Brandon explains, the most vulnerable and least mature organ in preemies is the brain, which also happens to be the center of circadian development. Because circadian patterns are linked to a healthy immune system and restful sleep patterns, she wondered whether using light to jumpstart the circadian clock in preemies could move them out of intensive care and into the arms of their parents faster than usual.
“You can’t treat preemies like fetuses anymore because their bodies are developing differently than if they were in the womb, but they’re not full-term, either,” says Brandon. “It’s tricky because babies are supposed to develop in a near-darkness environment, but they are also supposed to develop in a circadian environment.”
Brandon, a trained neonatal specialist, has always been fascinated by the extreme differences between the setting in which a baby has developed in the uterus and the one into which it is thrust after birth. “Nurses, by and large, control that new environment, because we’re in there providing care 24/7,” she says. “I’ve always wondered if we could maximize outcomes for our little patients by manipulating that environment in ways that don’t cost a lot of money and are not invasive.”
One way to prepare preemies for life in the real world is to expose them to the same cycles of light known to reset the circadian clock in grownups. Brandon’s dissertation research tested this approach by giving day/night-cycled light to three groups of babies at three different postnatal stages. She found the two that received early cycled light put on weight more quickly and trended toward having shorter stays in the hospital but showed no advantage in short-term development.
In a follow-up study, Brandon looked at the effects of light on smaller, sicker babies. This time, she saw no differences in weight gain, length of hospital stay, or long-term developmental outcomes. The last variable to test is sleep, likely the best and earliest indicator that circadian rhythms are beginning to develop. Brandon has already amassed a mountain of data on sleeping preemies, and she hopes the analysis will reveal a trend of more consolidated, restful sleep in the babies exposed to cycled light. Even barring the sleep results, Brandon has been pleased with the outcome.
“Other people have hypothesized that babies who are kept in near darkness have better developmental outcomes, and my data would not support that hypothesis,” she says. “In fact, none of the research that has been done with cycled light has shown anything that is harmful, only a trend toward positive outcomes.”
“Other people have hypothesized that babies who are kept in near darkness have better developmental outcomes, and my data would not support that hypothesis.”
Based on the work of Brandon and others in the field, the American Academy of Pediatrics now recommends the use of cycled light in the care of premature babies. However, Brandon estimates that half of nurseries still operate in darkness, as it can take decades for new ideas in medical care to take hold. In the meantime, she is working to solidify her own findings by adding in other factors that could be affecting the circadian clock in her subjects, such as hormones in mother’s milk that could trigger similar circadian patterns.
No matter how much Brandon and her colleagues learn about the effects of light on our underlying biology, there are even more questions yet to be answered. For example, are there other ways that light affects human behavior? If light is so important, how do organisms like cave fish manage to survive in complete darkness? And will we ever know exactly how sunlight turns plants green?
Researchers no doubt will continue in their endeavors to illuminate these mysteries of light, just as earthly creatures will continue to be drawn to the sun’s glow.