Dr. Ralph Mistlberger Reflects on 25 Years Studying Circadian Rhythms in the Department of Psychology at SFU
Dr. Ralph Mistlberger first encountered BC’s West Coast as many inspired youth did in the 1960s and 70s: hitchhiking across Canada and seeing the highways, countryside and ongoing development of Canada’s emerging urban centres like Winnipeg, Calgary, Edmonton, and Vancouver. Perhaps it was Mistlberger’s own experience growing up Anglophone in the tense social and political atmosphere of French-Canadian Montreal. He remembers that going “on the road” for a period of time is “what you did back then.” He also recalls being dropped off at a youth hostel at Jericho Beach at sunset on a balmy August evening and thinking, ‘this is where I want to live’.
Throughout the early 1980s, before making his way back to the West Coast, Mistlberger was a busy researcher: he completed his doctoral work on sleep and circadian rhythms at the University of Chicago, a post-doctoral fellowship at Dalhousie University, and was a senior research fellow at Harvard Medical School. In 1988, Mistlberger found a home at SFU’s Psychology Department, funded in part by a 5-year NSERC University Research Fellowship. At that time, Mistlberger remembers, SFU’s Burnaby campus offered a rare commodity, substantial lab space suitable for behavioural neuroscience research, including Mistlberger’s work on circadian rhythms.
Circadian rhythms are the behavioural and physiological changes in animals that follow a 24-hour cycle. These rhythms are not strictly evidence of a singular “biological clock”; rather they reveal a number of internal “clocks” responsible for synchronizing our behaviour and physiology to daily cycles of light and dark and also to significant ‘non-photic’ stimuli such as mealtimes, social interactions and imposed work schedules. Mistlberger’s lab played an important role promoting the view, based primarily on behavioural data, that there are multiple circadian clocks and that non-photic cues, especially food, may be more important than light for controlling the timing of many of these clocks.
In the mid-to-late 1990’s, a major breakthrough came about when researchers discovered the genetic basis of circadian clocks in mammals, and found that so-called ‘circadian clock genes’ were cycling in individual cells in many brain regions and most body organs and tissues. Apart from one master clock in the brain that is synchronized by light-dark cycles, almost all of the other clocks were found to be synchronized by the timing of food intake. This finding validated the ‘multiple clock model’ and Mistlberger’s view, shared by only a minority of other chronobiologists for many years, that when it comes to most daily rhythms, food is indeed the dominant time cue. Mistlberger admits to continued frustration that, despite years of study, they have so far been unable to localize in the brain the circadian clock that generates daily rhythms of foraging activity synchronized to regular mealtimes. He notes that because finding food is so important, the circadian clock that controls foraging in animals may really be a population of circadian clock neurons located in multiple brain areas.
Another recent advance that dramatically shifted the field was the creation of transgenic animals in which bioluminescence is used to visualize the cycling of living circadian clocks in multiple body tissues. Mistlberger describes a breed of mice that are genetically engineered such that the circadian clock in brain and body cells drives expression of a gene for making luciferase. Luciferase is an enzyme found in fireflies: it is that which that makes them glow, and in these transgenic mice, it causes the clock cells to glow with a daily rhythm. Observing these mice has allowed researchers to test and track the functioning of circadian rhythms through bioluminescence. Mistlberger’s lab is now using this method to understand how the timing of food intake, in combination with daily light-dark cycles, regulates daily rhythms in the brain and body. In addition to localizing brain clocks that mediate foraging rhythms, researchers are particularly interested in what happens when lighting and feeding schedules are shifted, as happens to humans following transmeridian jet travel and shift work rotations. These shifts are associated with internal ‘chronochaos’, with different clocks shifting at different rates and directions. Mistlberger’s lab is exploring strategies that can minimize or prevent chronochaos in mice, with the hope that this work will eventually translate to solutions to the problems faced by shiftworkers and frequent travellers.
“Real life” implications of Mistlberger’s research on circadian rhythms are dramatic: he and his colleagues have become increasingly interested and invested in the lives and experiences of shift workers, whose lifestyles often result in erratic sleep patterns and varied eating schedules. Mistlberger has already completed one report on Shiftwork Practice in BC for WorkSafe BC. In his own research and the work of his graduate students, researchers are finding that shift workers struggle with such problems as sleep deprivation, sustaining mental alertness, and metabolic disorders. Thus, one goal of studying the behaviour and activity of shift workers is to find reasonable solutions to the common challenges and health problems reported by shift workers to improve their overall quality of life. Mistlberger’s research and graduate supervision will continue with this in mind, adjusting and testing the impact of meal intake and light exposure, and finding new and creative ways to encourage synchronizaton and balance in the body’s circadian timekeeping system.