Josh Stuart was a CU undergraduate majoring in molecular biology in the mid-1990s when he discovered the power of computational analysis to reveal the functions of genes.
“I thought of computer science as the other side of the coin from biology,” he recalls. “In biology, the aim is to understand a complex system with simple rules, whereas in computer science the aim is to build complex systems using simple rules.”
After earning double bachelor’s degrees in MCD biology and computer science at CU-Boulder in 1996, he went onto Stanford where he completed a PhD in biomedical informatics, a field that marries the two disciplines. Now an assistant professor of biomedical engineering at the University of California at Santa Cruz, Stuart is the recipient of CU-Boulder’s 2006 Kalpana Chawla Outstanding Recent Graduate Award. The award recognizes alumni who have made exceptional contributions to their field within 10 years of graduation.
“The research opportunities provided by CU were the single most important factor in preparing me for graduate school,” Stuart says.
As an undergraduate, Stuart was involved in both molecular biology and computer science research. With MCD biology Professor Gary Stormo, he worked to decipher the code by which DNA nucleotides in a gene’s regulatory sequence promote the gene’s expression. With computer science Professor Elizabeth Bradley, he worked on harnessing mathematical chaos to teach a computer to generate human movement innovations such as in dance and karate. For his research, he was awarded both a Summer Cancer Fellowship from the CU Health Sciences Center and a fellowship from the Denver ARCS chapter.
“Josh is truly a rare talent—someone trained and skilled in two fields who gets both the subtleties and the big picture,” says Bradley. “He not only has a nose for good research problems and the drive to carry them out, but also the ability to infect others with his enthusiasm.”
Stuart, who also won the prestigious Sloan Research Fellowship in 2006, developed a new mathematical tool for the interpretation of gene activity which is based on the recommender systems used by e-commerce sites like Amazon.com. Stuart’s gene recommender suggests and ranks genes that have a high probability of being involved in a particular biological pathway based on a list of other genes already known to be involved in that pathway.
“There’s so much data that biologists have collected already, the discovery bottleneck is now in developing computational tools that can extract information from it,” he says. “Imagine what the Internet would be like without a search engine; hordes of useful information would not be able to be tapped. Molecular biology is still waiting for its Google.”
“In the area of cancer,” he explains, “we know a few of the genes that are major players in tumorigenesis, but many of these genes cannot be targeted with drugs. A search engine will allow us to scan for genes that act with the known cancer genes, allowing us to possibly identify additional genes amenable to molecular therapeutics. “
Stuart’s lab currently focuses on developing mathematical techniques for combining information across different species, such as humans and mice, to find clues about what genes do. (Over half of the genes in our genome have no known function.) High-throughput technologies developed over the last 10 years, such as DNA microarrays, are allowing investigators to measure the coactivity of genes on a genome-wide scale.
“If two genes are turned on together—not just in one, but in several organisms—then the two genes are very likely to function together because their coactivity has been conserved over millions of years of evolution,” Stuart says. His computational approach is to link genes together that exhibit such conserved coactivity, and his group then analyzes the resulting networks of genes for clues about how the genes function together.
At UC-Santa Cruz, Stuart works with some of the top researchers in the field of bioinformatics, including David Haussler, a CU-Boulder alumnus whose work was instrumental in the decoding of the human genome. Haussler received the college's Distinguished Engineering Alumni Award in 2005. “Lots of bioinformatics researchers have come from CU,” Stuart notes, adding that his own work could not be done until the sequences of different species were unraveled.
Stuart also is working with chemists who are extracting various microbes from sponges in the ocean to look at how these unknown compounds affect cells. The eventual outcome, researchers hope, will be to find new therapeutics while enhancing our fundamental understanding of biology.
“We’re still focused on finding one gene at a time; in the future I believe we’ll be able to investigate the way entire systems of interacting genes lead to disease susceptibility,” he says.