CHRISTIAN BURKS 

Slicing and dicing the facts of life 

Pamela Sherrid / US New and World Report 25dec00

Christian Burks spent a good part of the past four years hunting for an elusive fruit-fly gene that could lead to new treatments for human cancer. But Burks wasn't peering down a microscope or, indeed, doing anything traditionally considered biology. Instead, he led a team that used computers to sift through massive amounts of DNA data, then exploited mathematical tools to predict which of the fly's 13,000 genes was likely to be a tumor suppressor.

Burks is a top practitioner in the crucial new field of "bioinformatics," the marriage of information technology and biology. Thanks to rapid advances in deciphering the genetic code, scientists are generating an exploding volume of biological data that can be stored and analyzed only by computer–for instance, billions of bits of information on gene sequence, individual genetic differences, and protein structure. A bioinformatics specialist helps other scientists work more efficiently–the kind of behind-the-scenes role that usually gets little credit in science, where oversize egos are as common as in Hollywood. But being an unsung player is just fine with Burks, who grew up in low-key Colorado and disapproves of the cult of personality in science. Besides, with biologists drowning in a sea of information, rewards are flowing to data specialists who can throw a life preserver.

DNA midwife. Burks was present at the birth of the new discipline. In the 1980s, he was part of the team that created the DNA database GenBank, the public repository that now houses the sequences–the order of the basic genetic building blocks–of the human genome and that of 86,000 other species. With information on 13 billion bits of DNA, GenBank has become an invaluable resource to researchers worldwide.

Sequencing is just the start of a long road that scientists hope will lead to new treatments for diseases such as cancer and Alzheimer's. Today Burks, 46, is chief information scientist at Exelixis, a young biotech company in South San Francisco, Calif., that is trying to identify which structures and processes in cells could be the best targets for new drugs. "When you combine computational insights with laboratory experimentation," Burks says, "you get where you want to go faster."

When Burks was a graduate student in molecular biophysics and biochemistry at Yale, there was no program in bioinformatics. He learned his way around computers as part of his Ph.D. dissertation work on the structure of proteins. As Burks explains it, bioinformatics involves either modeling–using algorithms or mathematical equations to make predictions–or transforming raw experimental data into understandable data.

The specialty at Exelixis (the name is Greek for evolution) is comparative genomics. That means using model organisms such as the fruit fly, the worm, and the zebrafish–fast-breeding creatures surprisingly similar to humans at the genetic level–to learn more about the human genetic makeup and its role in disease. Exelixis experiments on the animals, seeing what happens if one gene is deactivated, for instance. Burks is the master slicer, dicer, and storer of the resulting data, aiming to maintain maximum flexibility for future studies: "We don't know what questions our researchers will want to ask of that data in the future."

Bioinformatics played a key role in one of Exelixis's main triumphs to date: the identification of that tumor suppressor gene in the fruit fly. The loss or deactivation of the human version of that gene, known as p53, is the single most common mutation in human cancer. Identifying the fly version would speed drug development by allowing experimentation on p53's function in cells. "Lots of scientists had looked for a long time in a very dedicated way for p53 in the fly and couldn't find it," says Burks.

The sequence of the p53 gene in humans is known, but a straightforward comparison with the fly genome sequence doesn't reveal the fly counterpart, says Burks. Did portions of the sequence change through evolution while letting the gene still maintain its function? To find out, Exelixis aligned the p53 genes of six species including the fruit fly, the human, the mouse, and the toad, seeking the gene with sufficient commonality in all the species.

Fly fruits. That alignment helped pinpoint the most promising fruit-fly gene. To make sure it was on the right track, Exelixis relied on another tool from its bio- informatic bag of tricks. Other scientists already had figured out the three-dimensional structure of the protein made by human p53. So Exelixis used computational techniques to figure out the three-dimensional structure of the protein created by its candidate fruit-fly gene. Sure enough, the structures were similar enough to convince Exelixis that the fly gene in question played a role in tumor suppression. "But informatics does not supply conclusive evidence," says Burks. The case wasn't closed until fruit-fly experiments showed that knocking out the candidate gene allowed mutated cells to proliferate.

Because of the intense demand for informatics specialists at biotechs and pharmaceutical companies, universities from Berkeley to Philadelphia are launching new programs in the discipline. But few schools are turning out graduates yet. To staff his department of some 25 people, Burks has had to find the odd birds who, like himself, are savvy in biology and chemistry as well as computer science and software engineering. "It's a small population," he says.

These days, Exelixis (and Burks) have more ambitious plans. Instead of merely identifying biological structures that play a role in disease, the company hopes to determine what chemicals could be used to develop drug treatments. Burks has to manage information on millions of chemical compounds, as well as come up with tools to predict how compounds will act in the body. Exelixis could start clinical trials of a new cancer drug as early as 2003–if all goes well with the relentless crunching of numbers.

March 1, 1999

Bioinformatics

Christian Burks, Ph.D.

source: http://mcb.berkeley.edu/courses/mcb294/march1.html 21 Dec 2000

Chief Information Scientist, Senior Director of Bioinformatics
Exelixis Pharmaceuticals

Christian Burks is Chief Information Scientist and Senior Director of
Bioinformatics at Exelixis Pharmaceuticals. He is responsible for
enterprise-wide information technology and computational biology
strategy, planning, and implementation. He established, developed, and
oversees the Bioinformatics Department, currently comprised of three
groups:

The Sequencing Resources Group provides a core, high-throughput
facility for all sequencing needs, using sequencing machines and
associated robotics, and with an overarching laboratory information
management system. This group also generated a unigene
database project based on assembled EST and other DNA sequence data
that represents the most complete representation of Drosophila genes
worldwide.

The Information Technology Group provides enterprise-wide computational
infrastructure, and is responsible for overall architecture and
strategy, internet access, computer security, external web site and
internal web infrastructure, desktop support (Unix, Mac, and PC
platforms), secure international WAN and internal LAN (over multiple
physical sites), and administrative applications. Also responsible
for the corporate library and literature retrieval system.

The Computational Biology Group is responsible for management and
analysis of molecular biological, genetic, and genomic data. They
have designed and built an extensive software infrastructure
centered on characterization of orthologous genes, proteins, and
pathways among target and model organisms. They are also responsible
for providing LIMS, quality control, and pattern analysis tools for
DNA sequencing pipeline.

Prior to joining Exelixis in 1997, Dr. Burks was at Los Alamos National
Laboratory, where he held positions as Group Leader for Theoretical
Biology and Biophysics and Program Manager for Computational Biology.
He led the GenBank database project as well as other database projects
there, and has published numerous papers on molecular biology databases
and finding patterns in DNA sequences.

He was educated in the Great Books program at St. Johns College (B.A.,
1976) and the Molecular Biophysics and Biochemistry Dep't. at Yale
University (Ph.D., 1982).