Assistant Professor Joshua Gooley is studying how light influences our circadian rhythms, controlling when we feel tired and when we feel awake. He told Vital Science about his research at the new Chronobiology and Sleep Laboratory at Duke-NUS, his dreams of designing jetlag-eradicating glasses, and how living in a room for 6 days can feel like a holiday.

Unraveling circadian complexities
Deep in the heart of Singapore General Hospital, people are frozen in time. They have beds but cannot sleep; they eat regular meals but do not know breakfast from dinner. There are no clocks, no natural light and no noise from the outside – the inhabitants exist in their own world, living life entirely on their own schedules.

Outside these 2 by 5 meter rooms sit the controllers, watching every second on a live video feed. The setup is state of the art, modeled on the latest technology from the US. But far from a prisoner isolation center, it is the sleep laboratories at Harvard Medical School that provided the inspiration. And with it came Assistant Professor Gooley who – as Assistant Professor at the new Chronobiology and Sleep Laboratory at Duke-NUS – hopes to finally deliver bedside applications to his research which began at the bench 10 years ago.

 
Assistant Professor Gooley poses in front of the Chronobiology and Sleep Laboratory’s wall-mounted ‘daylight simulator’ which is used to deliver bright white light therapy to research volunteers

Assistant Professor Gooley is a chronobiologist – a field devoted to studying the natural 24-hour circadian cycles which make us wake up and fall asleep. Many factors influence the circadian clock – food, exercise and drugs, for example – but he is focused on the effects of light. His breakthrough came with a 2001 paper in Nature Neuroscience, announcing that he and his Harvard colleagues had identified the putative function of an elusive cell in the retina containing a pigment known as melanopsin. Unlike rods and cones, which send information to the visual cortex to create a conscious image of the world, the melanopsin-containing cells connect directly to the suprachiasmatic nucleus – an area of the hypothalamus which houses the subconscious circadian clock. Controlling this pathway, therefore, could theoretically control our sleep-wake cycles – a concept with very useful implications.

“If you give the right amount of light at the right time, you can actually resolve the symptoms of jetlag,” says Assistant Professor Gooley. Bright light in the evening before flying, for example, would push the circadian clock backward and postpone tiredness, thereby helping someone who is heading west, he explains. Exposure to bright light in the morning, conversely, can shift the circadian clock forward, and would be beneficial before flying east. “Another major application would be to help a shift worker adapt to his schedule, or to design a workplace lighting environment which promotes alertness, increases productivity and improves safety. There have been studies in nurses showing that exposure to bright light on the nightshift and then dim light after leaving work helped them to adjust,” he says.

A bright future for light therapy
  The theory has already been put into practice in the form of light therapy devices, which have shown some success for the treatment of seasonal affective disorder and circadian sleep disorders. But users must sit and stare into the light for long periods to reap the benefits of therapy – an inconvenience which Assistant Professor Gooley aims to overcome. Different retinal cells respond best to different wavelengths of light and durations of exposure, he explains, suggesting that the process could be fine-tuned to maximize the activation of melanopsin-containing cells in proportion to rods and cones. If the devices could also be scaled down and made portable, then light therapy could become a powerful and practical way to tackle jetlag.
Sleep technicians Victor Pachas and Jonathan Bostick prepare volunteer Erna Tandiana for a research study
“I think the whole field should be gravitating towards these spectacle-based designs where you just put them on, go about your normal routine and still get the benefits without having to sit down and stare and disrupt your daily routine. That way, a businessman going across six times zones could put on his light therapy glasses and get an extra boost in the right direction before he gets to his destination,” says Assistant Professor Gooley, who is already working on the glasses with fellow Assistant Professor Aaron Danner, an engineer at NUS. He believes they are feasible, and that new design features will enable this technology to overcome problems with existing light therapy devices.

Living in the laboratory
In the shorter term, the first experiments at Duke-NUS will focus on how the different retinal cells interact to generate subconscious responses to light – not only their direct influence on the clock but also on other reactions such as pupil constriction and the release of the circadian hormone melatonin. The researchers are also looking at ways to measure internal body time using a single biological sample. Discovering an accurate, simple method could even help to improve drug efficacy and safety, by allowing doctors to administer a therapy precisely when it will have the greatest impact.
  
Research volunteers take computer-based tests that measure their attention and cognitive function in response to sleep loss and shift work schedules.

Ultimately, Assistant Professor Gooley hopes to look beyond light to establish how it interacts with the other factors that regulate circadian rhythms. But for now all external influences must be controlled – hence the need to keep subjects sheltered from natural light, physically inactive, and eating on strict schedules. Some will be deprived of sleep for up to 50 hours, but it is not the torture it may sound. They read, watch movies, and even play cards with the researchers to keep awake. And not all protocols involve sleep deprivation: some subjects will live alone for up to 6 days but be allowed to make use of the comfortable beds in the two newly opened research suites (according to fixed schedules, of course).

  Perhaps unsurprisingly then, there has been no shortage of volunteers since study recruitment began in August. One particularly enthusiastic student even phoned up within an hour of the first advertisement being posted.

“I think there’s a lot of intrigue about sleep studies. Some people are just genuinely amused by the whole experience because it’s so extraordinary,” says Assistant Professor Gooley. “Living in a time-free environment for three days sounds like an adventure of sorts. You have all your meals provided and you get to sleep in complete darkness and silence, which is hard to find in Singapore. Think of it like a little paid vacation – just one with a unique itinerary where you can’t actually go anywhere.”
Research Assistant Jonathan Bostick prepares a volunteer for light therapy, which is used to reset the body’s circadian clock and to enhance levels of alertness.