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Epigenetics researcher wins grant to study chronic fatigue

Prof. Patrick McGowan studies the role of environment in shaping physical and mental health.

Professor Patrick McGowan will explore the epigenetics of Chronic Fatigue Syndrome, a complex and debilitating illness that affects the brain and multiple body systems. He received a grant last week for the work from the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America.

McGowan, a professor in UTSC’s department of biological sciences and the director of the Laboratory for Epigenetic Neuroscience, conducts research into how environmental factors can change gene expression in the individual.

“Part of the way experiences get embedded in our biology is through direct changes to how our genes work,” says McGowan. “This is part of what’s become a paradigm shift in the way that biologists think about development.”

Our genes – the actual sequences of DNA that encode physical traits – are given to us at conception and never change. But between each gene and the trait it encodes is a complex series of mechanisms that read the gene and translate it into a protein. Many of these mechanisms are subject to environmental influences such as toxins, disease, or environmental stress. All of these have the potential to influence whether, when, and how some genes are turned on and off.

The CFIDS grant will allow McGowan to look specifically at the relationship between a system called the hypothalamic-pituitary-adrenal (HPA) axis and immune function. The HPA axis is involved in the regulation of the stress response, and also has effects on immune function and inflammation through cellular signaling mechanisms involving steroid hormones called glucocorticoids.

McGowan’s hypothesis is that there is an epigenetic change that disrupts glucocorticoid signaling in white blood cells called lymphocytes. By studying tissue samples of CFS patients he hopes to pinpoint the mechanism behind the change.

 One promise of McGowan’s research is that we may be able to change or reverse epigenetic effects through drugs or other interventions. An understanding of epigenetic changes might also determine which treatments are most likely to help an individual.

McGowan’s next research project will see him teaming up with Dr. Rudy Boonstra, professor of biological sciences at UTSC, in a study of snowshoe hares in the Yukon. Boonstra has charted the way hare populations fluctuate up and down according to how much pressure they face from predators. Hares reduce the size and frequency of their litters when stress from predators is great.

But Boonstra has also found that fertility changes persist for several generations after predation has dropped off. There seems to be an epigenetic change that is passed down to offspring and takes some time to wear off.

“It seems to be a kind of memory that persists across cycles. We think it may have something to do with a persistent memory of a genetic signal in terms of stress. We want to look at a true adaptation to the environment,” he says.

McGowan’s research offers exciting insights into the interplay between genetics and environment, says Malcolm Campbell, UTSC vice-principal (research). “There’s been a long-standing debate about the relative importance of nature and nurture,” says Campbell. “Research into epigenetics is giving us a detailed understanding of exactly how the environment works in combination with our genes to determine who we are.”

© University of Toronto Scarborough