A questioning mind and DNA analysis has led Dublin City University (DCU) scientist Dr Mary O’Connell to new insights about evolution … and polar bears. Claire O’Connell finds out more.
How can polar bears carry so much fat and still be healthy? Why don't naked mole rats get cancer? And how come some strains of the 'superbug' Clostridium difficile cause serious illness while their close cousins don't?
Those are some of the questions Dr Mary O'Connell has pondered recently, and thanks to a clever analysis of DNA, she has been turning up some interesting answers.
The polar bear's fab flab
She and fellow evolutionary scientist Prof James McInerney at NUI Maynooth were invited by the Beijing Genome Institute to work on the DNA analysis. It was initially based on a single polar bear but the project mushroomed to include a total of almost 90 polar and brown bears, she explains.
“It became a massive project involving collaborators in Beijing, Ireland, Denmark and UC Berkeley, and we made a list of questions we wanted to answer – where did polar bears come from, how long have they been on the planet, and how have they adapted to live in such a cold place?"
Close inspection of the DNA showed that polar bears as a species are relatively young – they split from brown bears around 400,000 years ago, when far more of the northern hemisphere was covered in ice than it is today.
But the real meat of the findings for O'Connell, who is interested in how animals adapt to extreme environments, is in the genes and pathways that explain how the polar bear can carry so much fat in its body for insulation and energy, eat an entirely fat-based diet and yet still be fit and healthy.
"The benign state of a polar bear is what could be considered morbidly obese," she says. "Yet they are not dying young from heart attacks and clogged arteries."
When the scientists dug into the polar bear DNA, they found genes involved in fat metabolism and cardiovascular function that appear to allow the bears to function efficiently with such enormous fat stores.
The findings are of relevance to human health, according to O'Connell. "These are pathways we would have suspected, they are involved in cardiovascular health," she says. "But now we know the specific genes that are tweaked in the polar bear, and we can look at what is going on with comparable genes in humans."
New insights on disease
O'Connell uses DNA and protein analysis to look at plenty of other organisms, too, particularly where there is an interesting take on disease. One superstar is the naked mole rat, a small and long-lived desert rodent that seems to be resistant to cancer.
"They have more or less the same number and types of genes we have, but certain of their copies of those specific genes have evolved in a particular way that protects them against tumours," she explains. "So we are looking at genes that we share with the naked mole rat but that are tweaked in the naked mole rat, and we are looking at how interesting new genes emerge in the naked mole rat genome."
O'Connell also works with DCU scientist Dr Christine Loscher on the bacterium C. difficile, which causes intestinal problems for vulnerable patients in healthcare settings. Their analysis is showing that proteins at the surface of the bacterium seem to make particular strains more virulent, or disease-causing, than other strains.
Mouse versus human
O'Connell compares the DNA of mice and humans, because mice are an important experimental model in medicine, and therapies that work in the furry creatures in the lab don't always translate into therapies that work in humans.
Understanding the fundamental genetic differences between the species could help us better predict how a medication might work in practice: "These are things molecular evolution can help with," she says. "The mouse has given us a huge wealth of information, but this is an extra filter for designing more species-specific drugs."
Embracing 'messy' evolution
While disease is a particular focus, O'Connell's overarching interest is in evolution, which she emphasises is a broad area. "Evolution underpins all of life, how everything works," she says. "And to work in the area I've had to be a biochemist, a molecular biologist, a mathematician and a computer scientist, I've knitted all these things together to get to the bottom of things."
O'Connell works on a range of questions, including when eukaryotic cells (like the ones we have) arose, when mammals got a placenta and how genes have influenced behaviour in evolution. DNA analysis has opened up whole new ways of looking at how species are related, she notes.
"It's about finding things that are similar across different organisms – we used to do that morphologically, classify on the basis of backbones or fins – but the more data we have from genomics and DNA, the more we see those classifications can be limited and can sometimes be misleading. It's not just a case of organisms descending from their ancestors and splitting, it can be messier than that and we have to build new theoretical frameworks to understand, capture and model the messiness," O'Connell says.
The key to science is asking questions, according to O'Connell, who reckons she has been a zoologist "since age five" and grew up devouring encyclopaedias at her home in Banagher, Co Offaly.
A degree in biotechnology from NUI Maynooth whetted her appetite for molecular evolution, and she completed her PhD there on how humans and mice evolved and adapted in their 200m years of independent evolution.
Now based in the Bioinformatics and Molecular Evolution Group at DCU's School of Biotechnology, she recently went on sabbatical to Harvard University on a Fulbright scholarship, where she expanded her studies to include birds. "It was amazing to work in that environment – even walking through the Museum of Natural History on the way in to work every morning was a dream," she says.
Her main advice to women with an interest in science is to have the courage to stand up and ask questions.
"I see it at conferences all the time – when it comes to question time, the first to ask are the men," she says. "So I'd say don't be afraid to stand up and ask the question you are interested in, whether it's in an international conference, a lecture hall or classrooms. Being a scientist is all about asking questions, so why sit back?"
Women Invent Tomorrow is Silicon Republic’s campaign to champion the role of women in science, technology, engineering and maths. It has been running since March 2013, and is kindly supported by Accenture Ireland, Intel, the Irish Research Council, ESB, Twitter, CoderDojo and Science Foundation Ireland.