More than 20 years ago, a group of scientists attending a conference at the University of California, Santa Cruz, daydreamed about the possibility of sequencing the entire human genome. Fifteen years later, on that very same campus, David Haussler, a professor of biomolecular engineering, and then-postdoc Jim Kent assembled the first complete version of the human genome using an algorithm Kent had written. Needless to say, they made headlines and history. It is no surprise, then, that Haussler has managed to attract some of the best and brightest graduate students and postdocs in computational biology over the years.
Since that time, Haussler, also a Howard Hughes Medical Institute investigator and leader of the Genome Bioinformatics Group at UCSC, has continued to make groundbreaking contributions to genomics. His current focus is comparative genomics, an increasingly large umbrella that includes the evolutionary history of the human genome and elucidating the different phenotypes that have emerged in human and other placental mammalian lineages through changes in genome sequence.
Katherine Pollard, a former postdoc, was a member of Haussler's lab from 2003 through 2005. Currently an assistant professor of statistics at UC Davis, Pollard worked with Haussler to compare the human genome to that of a chimpanzee, and in the process discovered at least part of why it is that we are so different from our closest evolutionary relative. Using a technique she developed, Pollard identified regions of the human genome that have undergone significant change over the last 6 million years. Twelve of these regions are thought to be directly involved in human brain development, which may explain why we evolved to be slightly more clever than our banana-eating cousins.
Pollard says it was the time with Haussler that transformed her from a biostatistician working on theoretical problems to being a full-fledged computational biologist. "After spending about six months in David's lab, I realized that there were problems that were inspired by questions in biology," she says. "Really I was working on the math and the algorithms — they had applications in biology, but I wasn't deeply involved in asking the biological questions."
It was in Haussler's lab that she learned to act like a biologist, while at the same time utilizing her computational and statistical skill set. "He taught me a lot of specific information about biology, but also how to think differently and ask interesting biological questions and be motivated by the answers to those — not just the methodology that you use," she says. "Now I think [my] work is truly interdisciplinary and applied compared to what I was doing before."
Pollard says that her time with Haussler left an indelible mark, informing her approach to how she interacts with her students today. "I've definitely seen myself writing e-mails to my students that feel like e-mails he maybe sent me at some point," she says. "Sometimes I find myself using phrases he used to motivate me in order to motivate my own people, so that was a great lesson to learn how to do that in a very positive way, rather than setting up harsh competition between people in the lab."
'That creative spark'
Haussler says that he looks for graduate students or postdocs who are truly captured by their research pursuits. "I look for that creative spark, passion — I'm really looking for someone who's totally taken and excited by the research opportunities," he says. "One hundred percent involvement, dedication, passion — that's the number one criteria." As a mentor, he feels that his job is to encourage rather than to dictate, but that doesn't mean he is any less invested in his students' success. "I try to do everything I can to create an environment and engage in discussions and just pursue with them whatever ideas come up and cheer them on as they make discoveries," he says.
Haussler draws much of his inspiration from his former mentor, renowned mathematician Andrzej Ehrenfeucht, currently a professor of computer science at the University of Colorado, Boulder. "Andrzej taught me that it's the science that matters; really go after the big ideas, and never to be constrained by disciplinary boundaries or worry about other people's expectations. You have to follow your instincts," Haussler says. "And I've tried to convey that same message to my students."
When students leave his lab, Haussler says, he wants to see them go out into the world with confidence built not just upon thorough scientific knowledge, but also on recognized achievement. "It's really important that they're out there speaking, writing grant proposals, and dealing with all of the issues," he says. "I recruit grad students to help me out with all aspects of what I do as principal investigator, so I try not to shield them from that," he says. "They're responsible for writing sections of grant proposals."
To do this, Haussler believes in the baptism-by-fire approach. He recalls how graduate student Adam Siepel once gave a presentation for the mammalian gene collection project to a distinguished panel including at least one Nobel laureate, learning firsthand how to handle himself in a high-pressure situation.
But more than anything, it's the simple enthusiasm and a desire for his students to flourish in the world outside of his lab that make Haussler such a successful mentor. "People say it's great if your advisor is a cheerleader," says Pollard. "Well, I think David gets the prize for being best cheerleader ever."
The list of former Haussler graduate students and postdocs reads like a Who's Who of bioinformatics. Here are just a few who have made their mark in the field.
Haussler cites this former postdoc as the person who invented methods of applying hidden Markov modeling to sequence analysis, protein families, and finding genes. He is currently a professor of bioinformatics at the University of Copenhagen, Denmark.
Although Kent actually got his PhD in biology from another professor, he did some of his most notable bioinformatics work with Haussler. Kent, now an associate research scientist in the biomolecular engineering department at Santa Cruz, is also known as the author of a little program you might have heard of: Blast.
An early bioinformatics entrepreneur, Kulp co-founded Neomorphic in 1998, which was later acquired by Affymetrix. He is currently an assistant professor of computer science at the University of Massachusetts at Amherst. Even before joining Haussler's lab, Kulp designed the first generalized HMM for gene finding, called the Genie System, used to find the genes in the Drosophila genome when it was sequenced in 1998.
After his graduate studies with Haussler, Noble developed a lot of applications to classify cancer samples by analyzing their gene expression. This was one of the key areas where support vector machines were applied, and HMM was used to discover motifs and a number of other innovations.
In 2005, Siepel published a paper that introduced the world to PhastCons, now a widely used tool for identifying evolutionarily conserved sequences. After his work with Haussler, Siepel became an assistant professor of biological statistics and computational biology at Cornell University.
Currently an associate professor of molecular and human genetics at Baylor College of Medicine, this former grad student was one of the first researchers to use the minimum description length principle to study transposons.