After just 5 years in Canada, Tim Hughes is already making his mark on the nation's biomedical research community. A full professor in the Banting and Best Department of Medical Research at the University of Toronto, this American emigrant already has been honoured, in 2001, with the Ontario Premier’s Research Excellence Award. He also claimed a Canadian Research Chair position in 2002, and in 2005, he won the National Cancer Institute of Canada’s Terry Fox Young Investigator Award. This year, the 38-year-old molecular biologist was promoted to full professor and added yet another feather to his hat, one of the brightest so far: a 2006 Howard Hughes Medical Institute (HHMI) International Research Scholars award.

Earlier this fall, Hughes--no relation to Howard--got word that he was one of 17 Canadians in a group of 39 international scholars to receive the award, which pays nearly $500,000 (U.S. dollars) over 5 years. “I got the impression very early on that this was going to be very selective and that it’s fairly exclusive, so I was quite surprised,” he says about winning the award. This year's pool included 546 applicants from seven Latin American countries and Canada. Hughes's winning research proposed using microarray techniques to compare the genomes of a variety of vertebrate animals to test for common regulatory elements that determine gene expression. Using computational data analysis, Hughes hopes to create evolutionary trees of these genes and regulatory mechanisms in order to figure out how they work together to make cells function and how they contribute to the physiology of the organisms they are found in.

Getting moored

Hughes attributes his rapid rise to three simple tenets that have informed his professional choices: Work with passion, work hard, and--most important, he says--“always tackle the big problems first.”

The first big problem Hughes remembers tackling was what career path to choose. As he earned back-to-back bachelor's degrees in music and then engineering at the University of Iowa, Hughes felt adrift. He struggled to find a field that would fully engage him while also offering exciting career prospects--a story familiar to many scientists. “Music was just for fun, and then I ended up finding engineering too dry, and so I just couldn’t see myself staying with it,” he says.

During this period, he became interested in cell and molecular biology thanks in part to discussions he had with a roommate about his graduate research in Iowa's microbiology program. He was fascinated by a talk one of his engineering professors gave about high-performance computing in the Human Genome Project, and he began to see other connections between biology and engineering. “The exciting thing for me was the realization that cells are in essence mechanical/electrical machines, so the same principles that apply to engineering control systems seemed also to apply to cells,” he says. So he decided to go to graduate school to study biology.

Hughes matriculated in the cellular and molecular biology program at Baylor College of Medicine in Houston, Texas. At Baylor, he studied telomere replication proteins in yeast. While he was there, he says, he didn’t think too much about his career ambitions, but he did learn the importance of getting a good publication record. “It became very clear to me that in order to graduate, you had to produce at least a couple of high-quality papers or at least have a substantial body of work that was of high quality and would clearly be published shortly after graduation,” says Hughes. While in graduate school, he published four papers, two of which made it into Science. On one of those papers, he was "co-first author"; he was second author on the other. He finished his Ph.D. in 1998.

Gaining momentum

Four grad-school publications, including those two in Science, earned him a quick postdoc offer from a small-but-growing biotech firm, Rosetta Inpharmatics, located in Kirkland, Washington, just outside of Seattle. (Rosetta has since been acquired by Merck.) “It was really the golden era for start-up companies. They had a lot of money and managed to predict the future. There were teams of engineers, computer scientists, and biologists that were working as one, and [we] were all fired up about what we could do,” Hughes says. He worked there for 3 years, continuing his research on telomeres and pioneering the microarray techniques that form the basis of his international reputation. Once again, his work was documented in high-profile journals, and this time he claimed top billing. “We published a couple of high-profile papers in Cell and Nature Genetics where I was first author,” he says. One of these, his most influential, outlines his original use of microarray expression profiles as a phenotypic footprint for gene function.

Hughes never planned to stay in industry. “All I wanted to do is learn how to use microarrays and figure out how cells work”--then move on to a faculty position. Still, his industrial experience yielded benefits, he says--he learned how to work in interdisciplinary teams on large-scale projects, and that knowledge has since proved valuable.

Breaking down barriers

The knowledge gleaned from industry, a few big ideas, a few high-profile publications, and a good interview helped him land his current job at the University of Toronto in 2001. “What made him stand out at the time was his incredible piece of work he had done, and when he came and gave his seminar, I think people were just stunned,” says Brenda Andrews, chair of the Banting and Best Department of Medical Research. “It was just a beautiful piece of science that everybody simply just had to recognize.” Once he was hired, Andrews and her colleagues noticed Hughes's talent for working across disciplines and speaking the languages of a variety of fields. “That’s another way of thinking big," Andrews observes. "Sometimes you need to talk to people who may not understand your language to make the next big leap.”

The HHMI International Research Scholars Award

In the 15 years since its inception, the HHMI International Research Scholars award has given 74 Canadian researchers nearly $30 million. This year, Canadians submitted more than 200 applications, for a 10% Canadian success rate. Applications undergo several stages of scientific review, which take about a year to complete. “We prize innovation and creativity,” says Jill Conley, director of HHMI’s international awards programs. Although many supporters of scientific research are risk-averse, she says, HHMI encourages researchers to take chances and try new things. “Once you receive the award, you don’t have to stick to your original proposal. You can go wherever your nose takes you,” she says.

There's no denying that Hughes's history of success in science helped him win the award, but he believes that his willingness to take chances was the clincher. “We started working on vertebrates about 4 years ago not knowing anything about animal physiology, and we just started learning as we went along.” Hughes says. “If you shy away from something that might be painful, or if you’re scared to take risks, then that lowers the probability of doing something interesting. Everything that you do is a bit of a gamble.”

“It’s like evolution,” he says. “There’s no real goal at the end of evolution; it’s just learning to go with the punches.”

Andrew Fazekas is a correspondent at Next Wave and may be reached at afazekas@aaas.org.

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Andrew Fazekas is a correspondent at Next Wave and may be reached at afazekas@aaas.org.