Unravelling the mysteries of sleep

By Drima Chakraborty, Writer, and Chua Li Min, Science Writer
Joshua Gooley
Joshua Gooley on one of his regular hikes // Credit: Joshua Gooley

Joshua Gooley did not dream of becoming a sleep researcher, but it was his dreams that ultimately steered him in this direction.

“I first became really interested in sleep when I was a teenager, because I was fascinated with dreams,” said Gooley who often had lucid dreams or dreams in which he could control the content. “The lucid dreams that I had were pretty frequent, and they really piqued my interest in sleep and dreaming.”

Despite having a variety of interests, Gooley, a liberal arts graduate, found himself gravitating toward the sciences. While applying to graduate schools, he made the pragmatic decision to research his options so that he would give himself the best shot at getting into a programme of his choice. 

“When I applied to the Neurobiology programme at Harvard Medical School, I knew from my research that they had the largest division of Sleep Medicine in the United States,” he said. “So I included in my letter that I’d be interested in pursuing a PhD in Neuroscience—that I’m interested in sleep, and named a couple of the professors.”

The statement garnered interest among the faculty. “I was contacted by one of them, a real fatherly figure who guided me towards sleep research.”

Gooley’s fate as a sleep researcher was sealed after he accepted the offer from Harvard. Looking back, the Associate Professor with the Neuroscience and Behavioural Disorders Programme at Duke-NUS said, “I like to reflect on how, what seemed like a small decision at the time, ended up being a major life decision.”

Nurturing a bright spark

That fatherly figure was Charles Czeisler, Baldino Professor of Sleep Medicine and Director of the Division of Sleep Medicine at Harvard, a legend in the field of circadian rhythm and sleep medicine whom Gooley spent his postdoctoral career with.

But before working with Czeisler, Gooley joined the laboratory of Clifford Saper, the James Jackson Putnam Professor of Neurology at Harvard, on a rotation project.

Another giant in the field of sleep neuroscience, Saper remembers Gooley’s aptitude and passion for research.

“The key question I ask graduate students and postdocs who want to work in the lab is what experiments they would do if they could do anything they wanted and had all of the equipment and supplies and expertise necessary. Most of them look like deer in the headlights,” said Saper.

But not Gooley. He already knew what he wanted to work on.

“Josh answered right away that he had read that there was a new photopigment, melanopsin, and he wondered whether it might be involved with relaying light sensitivity to the suprachiasmatic nucleus [a master clock in the brain],” said Saper.

Proving to be exceptional

It took Gooley less than six months before he submitted his work to the prestigious journal, Nature Neuroscience.

On 1 November 2001, the journal informed Saper and Gooley that their manuscript would be accepted if they could revise and submit it by 3pm the very same day. After rushing to revise the manuscript, Gooley’s first paper was finally accepted for publication in the December edition of Nature Neuroscience when he was only 23.

“While I had faced many deadlines before, this one really stood out because of the urgency—there were other researchers about to publish similar work,” recalled Gooley.

Saper was impressed by Gooley’s progress, referring to him as an “exceptional student”.

“Most students will struggle finding their own project, which can take a year or two, then in collecting the data and writing it up,” said Saper.  “It is unusual to have a publication in the first two or three years. I have never had a student before who came up with his own project on entering the lab, or one who was able to produce a definitive answer in less than six months!”

While he may already have had a prestigious publication under his belt, Gooley was far from done. After observing that rats in the laboratory changed their circadian rhythms to anticipate food, Gooley traced the origins of this change in specific circuits in the brain, which earned him a second Nature Neuroscience paper.

After working mainly on animal models for his PhD, Gooley joined Czeisler’s laboratory as a postdoctoral fellow, where he got to work with his preferred subjects, humans.

In Czeisler’s laboratory, Gooley delved into the function of retinal ganglion cells (where the photopigment melanopsin is found) in people. Here, he discovered that cone photoreceptors in the eye coordinate with melanopsin to control the biological response in humans to light, which could be used to treat sleep disorders.

Crossing time zones to continue his research

By 2007, Gooley had made a name for himself in Boston as a promising young circadian biologist studying how the brain synchronises major organ systems in the body to respond to changes in the environment. And it was time to find a junior faculty position as well as new home for him and his wife, whom Gooley met when they were both undergraduates at Wesleyan University.  

“It made sense to consider Asia because my wife is Asian and her family was in Southeast Asia and Singapore,” said Gooley.

When his brother-in-law caught wind of a new medical school that was hiring back then, “he sent the message our way, just as a heads-up,” added Gooley.

“At that time, Duke-NUS was really young so the building that I’m in now—where I am now— didn’t exist at the time that I was applying,” recalled Gooley.

En route to Australia for a conference, Gooley stopped off in Singapore for an interview and about a year later, he joined Duke-NUS—where he set up the Chronobiology and Sleep Laboratory to continue his research on sleep and circadian rhythms. 

Joshua Gooley and wife

Gooley (right) with his wife on his graduation day in 2006 // Credit: Joshua Gooley

Finding out what makes someone tick

“Sleep influences all aspects of your physiology and performance,” said Gooley, who is on a mission to understand what drives poor sleep habits and how such habits can be corrected.

He devised a two-pronged strategy—one that is both data- and research-driven to answer his question.

As the research team lead looking into the neuroscience of education at the NUS Institute for Applied Learning Sciences and Educational Technology (ALSET), Gooley uses the existing database at ALSET to study how school start times impact students’ sleep patterns.

Through analysing the login behaviour of students to NUS' learning management system—Gooley was able to determine when students were awake and when they were asleep.

He was careful to ensure that the data was comparable with that obtained using an accelerometer—a wristwatch-like device with a motion detector and light sensor that is traditionally used to measure the sleep-wake cycles—before adopting this data mining approach for studying sleep patterns.

“That data set was incredibly powerful, because it allowed us to map the window of sleep opportunity in students for different class start times,” explained Gooley, who now uses it to study how sleep patterns affect the wellbeing and performance of students.

There is also a special facility where all the other research takes place. In this sleep lab, the effects of sleep deprivation are studied through sleep studies conducted on human subjects. Other than looking at sleep deprivation, Gooley also uses these sleep studies to understand how certain environmental cues such as light affect the sleep-wake cycle.

Sleep Lab

A participant performing a psychomotor vigilance task (PVT) during an in-lab sleep study, which measures behavioural alertness in individuals by determining their reaction time in responding to a visual target onscreen

He does all this with the strong support from his team of dedicated staff who are equally committed to his mission.

“He’s actually so enthusiastic about the projects we have in the laboratory—he automatically infects everyone else with that enthusiasm,” said Dr Rukmini Dhara. “Everyone is invested in things succeeding because when you talk to him, you know that to him it’s not just a job,” added Rukmini, who completed her PhD project with Gooley before joining his laboratory as a research fellow in January 2018.

Gooley & his son (seated) with his lab in 2019

Gooley & his son (seated) with his lab in 2019 // Credit: Joshua Gooley

Coping during the pandemic

When COVID-19 hit Singapore’s shores in February last year, Gooley’s laboratory, like many others, was affected. With the sleep lab located within the Singapore General Hospital, they could not continue with their studies.

“We had an extended hiatus from doing lab-based research,” said Gooley on the six-month disruption faced by his team.

Instead of letting projects come to a standstill, he kept things running by getting his team to analyse existing data sets. “It’s not like we weren’t doing anything it’s just that we weren’t doing what we had planned on doing,” added Gooley.

In the midst of all the uncertainty, Gooley also saw the opportunity to use the research tools in his laboratory to address pandemic-related concerns. Making use of the Wi-Fi connection data from ALSET, he worked with his PhD student, Yeo Sing Chen, on a project to study how e-learning practices at NUS affected the clustering behaviour of students on campus.

At the time, Yeo was working on his PhD project looking at the impact of school start times on sleep and class attendance in students. Part of his project involved using Wi-Fi data to confirm the attendance of students in class. Using the same Wi-Fi data that he had analysed, Yeo proceeded to determine the number of student clusters on campus for the e-learning project.

In less than two months, the duo came up with a mathematical relationship that showed how the number of student clusters could be minimised.

“It was not a very big detour,” said Yeo, on having to switch tracks to look at student clustering behaviour in NUS. “I think the project was a good one as it had provided the university management with insights on their decision.” 

ALSET director, Laksh Samavedham agrees: “This [project] has helped validate some of the decisions taken by the university management in light of the COVID-19 pandemic with respect to the usage of classroom spaces and maximum class size for students to meet face to face safely, while moving the rest of the teaching and learning online.”

Other than ensuring that the laboratory’s research was ongoing during the pandemic, Gooley also kept an eye out for his team, keeping everyone connected through regular meetings while they worked from home.

“Josh is always there,” said Rukmini.

Drawing inspiration from daily life

When he is not in the laboratory, Gooley remains curious about the world around him. It was how Gooley ended up looking at variability of lipids in breast milk, with his long-time collaborator, Professor Markus Wenk who heads the Department of Biochemistry in the Yong Loo Lin School of Medicine in NUS. “That part of my research programme was guided by life events,” said Gooley.

“This was around the time that my wife and I had our first kid. I became interested in breast milk, all of a sudden, because it’s relevant for my life,” recalled Gooley. “I asked Markus, do you want to collaborate again? And he went—let’s do this,” added Gooley on how it began.

Prior to this, Gooley had already worked with Wenk on examining the effects of sleep deprivation and circadian rhythms on lipids in the blood. Tapping Wenk’s expertise as Director of the ‘Singapore Lipidomics Incubator’, it was the first study to use a lipidomics-based approach—a method which measures the different types of lipid species in a single sample to determine how lipids are regulated by the body’s biological clock.

This time round, Gooley and Wenk found that milk produced in the evening had a higher lipid content compared with that produced in the morning. Other than being regulated by the body’s biological clock, Gooley believes that the mother’s feeding pattern could also affect breast milk production. 

“It’s a neat study, because it shows, for the first time that what’s in breastmilk actually changes quite a lot depending on the time of the day,” said Gooley.

Outside of the sleep laboratory

Even before embarking on his research, Gooley was well aware of the importance of sleep.   When asked about his own sleeping habits, he replied: “I've always looked after my own sleep.” This was one thing about Gooley that stood out to Rukmini. She recalled how she first found out about his research at the Duke-NUS Open House, where he was giving a talk.

“Here is this guy—he’s talking about sleep and the importance of sleep,” said Rukmini. “So I raised my hand and I asked, ‘So you’re telling us about the importance of sleep, but how many hours, do you sleep?’ Then he replied, ‘I sleep for 8 hours.’”

“I’m very sensitive to sleep deprivation,” explained Gooley. “Because when I didn’t get enough sleep, I felt awful,” he added.

It is a habit he tries to cultivate in his two children. “I do put them to bed earlier,” he said. “We try to have our kids in the bedroom by 8.00pm and then they probably are asleep closer to 8.30pm.”

Being a sleep biologist, Gooley couldn’t help but notice differences in the sleeping habits of his children. “My son doesn’t sleep as much. He just doesn’t and he seems to be perfectly fine, so I’m not trying to make him sleep more,” said Gooley, who acknowledges it is not possible to have a one-size-fits-all approach when it comes to how much sleep an individual should get.

“With all the guidance that we give, it’s for the average person, the average child,” he said.

But pandemic or not, Gooley’s work on sleep is far from finished, and he already has plans laid out for studying the role sleep plays in learning.

“I think it’s important to follow something that you're really passionate about,” he said.

“You have to find a niche, you have to find the thing that you hope to excel at and it has to be something that you are really thirsty to learn more about. You have to be hungry to know the why of what you're doing, but I think a lot of people go through their lives, their careers not necessarily feeling passionate about what they are doing.”

Gooley with his wife and two kids at a picnic

Gooley with his wife and two kids at a picnic // Credit: Joshua Gooley

Gooley with his family at Gardens by the Bay

Gooley with his family at Gardens by the Bay // Credit: Joshua Gooley

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