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Genome Explorer Delves into Dark Matter

  • Title: Assistant Professor, Departments of Developmental Biology and Computer Science, Stanford University
  • Education: PhD, School of Computer Science & Engineering, Hebrew University, 2004                 
  • Recommended by: David Haussler

In his year-old lab at Stanford University, Gill Bejerano is a modern-day explorer. He investigates what he calls the “dark matter of the genome,” those functional, yet non-coding, regions of the genome. “I like vast open spaces that are previously less explored,” says Bejerano.

He is now working to fill in some of that space by using computational and functional assays to determine what these mysterious regions of the genome do.

Though he started out with a doctorate in computer science, Bejerano threw himself into learning biology when he joined David Haussler’s lab at the University of California, Santa Cruz, as a postdoctoral researcher. “I did a pretty big, I would say, switch of fields,” says Bejerano. Now a computational biologist, he starts by comparing the human genome to the other 20 or so assembled vertebrate genomes, from other primates and further on down the evolutionary ladder.

“By comparing to all these other genomes, you can start seeing the functional landscape of the human genome for what it really is — and then you start really appreciating how much out there does not code for protein,” he says.

Then, Bejerano hunts through specific sections of the genome locus by locus, functionally assaying them using transgenic mice and other animal models. He hopes that combining these approaches will lead to an overarching view of how the genome functions. “The appreciation you get is that it seems a large fraction of what is encoded in our genome is clearly functional, does not code for protein, [and] actually somehow orchestrates together when and where the proteins get turned on. It’s all about gene regulation,” he says.

Even with all these tools and knowledge, scientists still don’t quite understand how the genome is all put together. “The genome is only starting to unravel itself to us,” says Bejerano.

Looking ahead

But in the next few years, Bejerano imagines that the genome will keep on unveiling itself. Researchers, he says, will be getting better and better insights into gene regulation — a field they once thought they had all figured out. Biologists understand prokaryotes and unicellular eukaryotes pretty well, says Bejerano, but when it comes to invertebrates, “we have very little clue of what is actually going on.” The technology is out there for scientists to make headway in the next five to 10 years, he says. But a still nonexistent tool that would greatly speed up his own work would perform high-throughout genetic assays in mice, he adds.

Publications of note

As a postdoctoral fellow in Haussler’s lab, Bejerano was the one who, in 2004, found ultraconserved elements in the human genome. Far from being lost over time, these elements remain constant between humans and other mammals — and scientists still have no knowledge of their function or evolutionary history. It took Bejerano a while to fully appreciate what he and his colleagues had found, he says. “I think we were extremely fortunate to have the phenomena ... wait for us to figure it out. The more I dove into the literature, the more fortunate I felt. I really think those regions challenge us to this day. It’s a pleasure thinking that I came across the first,” he says. That discovery grew into a paper published in Science in May 2004. “That one, in some sense, would be hard to match,” says Bejerano.

And the Nobel goes to...

Bejerano wants to win for what he loves to do. “I really want to be able make a meaningful contribution to my field,” he says.