New faces at McGill (Page 3)

Looking at diet and spermatogenesis

Sarah Kimmins of Animal Science wants to prevent disease through diet — of the father!
Owen Egan

Patrick McDonagh

"Men should definitely be eating their greens," says Sarah Kimmins, newly appointed to the Department of Animal Science. The Halifax native, who completed her doctoral research at Dalhousie University, comes to McGill after a post-doctoral stint at the Institut de Génétique et de Biologie Moléculaire et Cellulaire in Paris. "If you are an underfed mother, your child has a greater chance of developing diseases later in life. We've known for a long time that food and drugs can have very serious consequences for developing embryos, and now we are discovering that later-life diseases can be caused by epigenetic modifications, which can be influenced by the environment — such as what you eat. For instance, a high-fibre diet changes the epigenetic mechanism of genes and can offer protection against colorectal cancer."

Hence the greens. But why men? Kimmins's research focuses on epigenetics — a second level of hereditary instructions coded within histones, which organize the DNA and make up chromatin. The epigenetic layer controls whether genes are turned on or off, thus playing a pivotal role in how our DNA works. Her research looks specifically at sperm cell differentiation to determine if it is sensitive to diet. "Can you manipulate diet to reduce chances of offspring becoming sensitive to disease, and is there an optimal diet that men should be eating to confer the greatest genome stability and the best chance to their offspring? Women are always told to make sure they consume enough folic acid — found in green vegetables — if they are going to conceive. Men probably should too." Spermatogenesis — when sperm is being created — involves a resetting of epigenetic marks in the germ line. "This period should have a window that is particularly sensitive to diet. Males constantly produce germ cells, so what a man eats may alter epigenetic patterns on histone during spermatogenesis and thus have long-term consequences for his offspring."

Consider the following scenario. A diet lacking in folic acid or a high fat diet leads to an accumulation of aberrant epigenetic marks on histones, such as those that prompt compaction of the chromosomes. If the chromosome is too compacted, it becomes inaccessible to other proteins that might be required to regulate gene expression. Such a scenario could lead to a lack of expression of genes required for sperm cell differentiation, which may translate into fertility defects. "In other cell systems we've seen that if you have a gene that should be turned off — perhaps a gene that promotes cancer — then you require methylation, which closes up space on the DNA strand, to be switched off. And the methylation can be influenced by your diet," she explains.

Kimmins's current research follows from her post-doctoral activities, where she used transgenic mice to study spermatogenesis. "I enjoy doing something that might translate into medical or preventative knowledge that could make a difference to people," she says of her work. "I was really attracted to it for that reason."

Even before going to France, Kimmins had her eye on McGill. "The university has a really great tradition of reproductive biologists, especially working in spermatogenesis, and very strong research teams studying environment-epigenetic interactions, which are both connected to my research." Kimmins has already begun collaboration with Jacquetta Trasler, a professor in McGill's Department of Pharmacology. "Trasler has shown that changes can be made in DNA methylation based on diet and drug treatments, but we don't know what happens at the histone level, so I'll be focusing on that. It's worked out really well."

Protecting our babies' brains

Catherine Limperopoulos' research into the cerebellum has shown how injury to that area can impair higher cognitive functions
Claudio Calligaris

Neale McDevitt

Talk about swimming against the tide. Catherine Limperopoulos is one of those rare health care professionals who was lured away from the U.S. to work in Montreal. Limperopoulos's journey to McGill, as Canada Research Chair (CRC) in Brain and Development, is perfect in its circular symmetry.

A native Montrealer, Limperopoulos did all her studies at McGill, including a PhD in research science. From there she pursued her post-doctoral work at Boston's Children's Hospital, where she participated in cutting-edge research using advanced magnetic resonance imaging (MRI) technology to study babies at high risk for brain injury, like preemies, and full-term babies who suffer some sort of brain injury before, during or soon after delivery — often due to a lack of oxygen. In particular, Limperopoulos is interested in the causes of injury and the consequences it has on subsequent development.

The program and technology is so advanced that there is nothing comparable in Canada. But not for long. Limperopoulos was invited to come back to her hometown and help her alma mater set up a similar program at the Children's Hospital. She jumped at the chance. "I knew it would be a challenge because this will be unique to Canada," says the new addition to Neurology and Neurosurgery and The School of Physical and Occupational Therapy. "But I'm glad to be able to bring it home and make it accessible to others with similar interests."

By Limperopoulos's calculations, the next six months will be spent acquiring and setting up the necessary equipment. On top of the CRC, Limperopoulos won an equipment grant from the Canadian Foundation for Innovation. "These funds will enable us to upgrade our scanner and set up a similar infrastructure to that in Boston," she says.

"From there, the idea is to use quantitative MRI techniques that enable us to measure and study brain injury in these children and to evaluate both the process of injury and the recovery time," she continues. The technology will give researchers the ability to establish concrete measurements quantifying brain growth in healthy babies and use that as the baseline against which to compare children with brain injuries.

As well, the technology gives researchers an objective way of evaluating various types of therapeutic and rehabilitation approaches. "By using the MRI before we initiate therapy, and again after a defined period of time using a targeted rehab technique, we'll be able to measure its effectiveness in terms of how the brain is wiring," she explains.

Like the events that led her away from, and then back to, McGill, Limperopoulos's research path has come full circle. Her doctoral training at McGill focused primarily on following high-risk infants and monitoring what happened to them over time. "I started looking at the consequences of brain injury, but now I'm trying to go to the very beginning and study the causes of brain injury. I hope that this will give me a fuller understanding of the issue." The long-term goal, of course, is to gain a better grasp of how and why injuries occur in order to prevent, or at least minimize the damage.

When asked how difficult it is to work with sick children, Limperopoulos pauses. "The biggest challenge is knowing where to draw the line. How do you best address research questions that involve critically ill babies while ensuring that the babies' safety and well-being is never compromised?" she asks. "Yes, an injury at such an early stage is so traumatic, but the amazing thing about babies is that their system has plasticity and is capable of reorganizing itself."

Idols of the idle

English professor Tom Mole picks Lord Byron as his first case study in the history of celebrity
Owen Egan

Maeve Haldane

In high school, Tom Mole carried about Byron's "Don Juan" like a dandy's gold-topped cane. "I thought it was the funniest, most brilliantly written poem I'd ever come across," says Mole, in his office in the Department of English.

The London-born Mole, the first in his immediate family to go to university, always assumed he'd study Lord Byron (1788-1824) in depth, but it wasn't until his graduate studies at the University of Bristol that he seriously cracked the book spines of the Romantic-era wit. A more mature look at the poet led Mole to thinking less about Byron's product and more about the product of Byron.

Byron enjoyed an unprecedented celebrity and fame, previously the domain of those who did great deeds, had high social standing, and were, uh, dead. "Real fame was thought to be posthumous fame," says Mole, but Byron was enormously popular while he was alive — his poem "The Corsair" sold 10,000 copies in one day.

It's not that Byron was the David Bowie of his generation, but that a range of emerging social factors and technologies set up the conditions for Byron's celebrity.

There was increasing literacy among the masses, who were sufficiently leisured and sufficiently moneyed to buy and read poems, and a better infrastructure for getting books and pictures to people.

As well, his image was marketed vigorously, Mole says, thanks to the portraits Byron commissioned. "They circulated widely in engravings, and every time they're engraved — there's no copyright — they change a little bit. Then they start to appear in caricatures and other kinds of graphic satire." It didn't take long for pictures that portrayed Byron with an open collar and curling forelock to circulate widely.

Unlike a commissioned painting, anyone can buy an engraved image to possess and "consume" in the privacy of their own home. "What's key to Byron's celebrity is the intimacy his readers feel," Mole says. "When you're reading a Byron poem, looking at a Byron picture, reading a biographical sketch in the paper, when you're consuming Byron's celebrity image, it feels like you're having a kind of relationship with the poet."

By drawing the connections between the poetry and his life, Mole says, "each reader believes that they alone are the one who understands Byron."

Also, with the surge in printed material at the end of the 18th century, writers and readers became less known to each other. Culture needed to find a way for texts to bridge that gap. Byron's poems avoided the impersonality of mass-produced products by constructing an impression of intimacy.

Byron had a knack for always seeming to reveal something about himself in his work, in a veiled dance of reveal and conceal, Mole says. "He always left the reader something to imagine. And he could always write another poem that could reveal a little bit more — it kept readers coming back."

Byron was merely one part of a celebrity-making machine, says Mole. "It's about Byron, his publisher, newspaper journalists, artists, engravers, caricaturists, printers, magazine publishers — a whole cultural apparatus."

Now that Mole is happily settled in to the "vibrant university culture" at McGill, he wants to tackle the history of celebrity, using Byron as the first case study.

"We're obsessed with celebrity," he says, citing the global success of TV's American Idol and its knock-offs, which purport to uncover people's inner brilliance or manufacture them into stars. The fantasy is that anyone can become a celebrity (ironically, the program's format is far more successful than anyone who's come out of it).

"Celebrity culture has an investment in us not thinking about it, remaining mystified. As long as we attribute the public profile of an individual to their talent or innate star quality, celebrity culture continues to work untrammeled.

"Only by thinking of that history, will we be able to engage critically with celebrity culture now."