BU College of Engineering Magazine
Spring 2004

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Life Sciences at Boston University
Research and teaching in the life sciences—including biomedical engineering—are increasingly prominent components of BU’s mission.
By David J. Craig and Tim Stoddard

Now that the human genome, that vast trove of genetic information encoded in our DNA, is only a mouse-click away, researchers face the daunting task of figuring out how tens of thousands of genes choreograph the life and death of cells. Under the leadership of Charles DeLisi, Arthur G. B. Metcalf Professor of Science and Engineering and senior associate provost for bioscience; faculty in the College of Arts and Sciences; the School of Medicine; and the College of Engineering are developing new ways of understanding the complex machinery inside living cells.

“We now have the full text for many genomes, but the text for the human genome has not yet been completely parsed into words,” says DeLisi, who is considered the father of the Human Genome Project. “When it is—and we can reasonably expect to be 90 percent complete in the next three to five years—we’ll have a parts list. We’re also developing the tools to understand how those parts interrelate. It’s not like putting together a jigsaw puzzle or a 747. It’s harder than that, because connections between the parts are not fixed—they change in response to the environment. The study and design of such complex adaptive systems is a major research area of modern engineering.”

Following is a look at some of the newest programs in genomic research at the University and specific work being done by Boston University researchers.

Program in Bioinformatics

As genomics has changed the biological landscape, Boston University has launched a graduate program to train rising scientists for leadership in the burgeoning field of bioinformatics. Founded in 1999 with a grant from the National Science Foundation’s Integrative Graduate Education and Research Traineeship Program, this University-wide program provides a unique interdisciplinary perspective on the science, engineering, medicine, and ethics of 21st-century cell biology. “To most of us, bioinformatics is a way to understand the cell as a system,” says DeLisi, the program’s director. “It’s the intersection between computer science and genetics. It’s a way to identify the functions of thousands of genes much more rapidly than we could have in the past.”

The program comprises 50 faculty members, and its thrust is integrating biology with information sciences and engineering. But there is also a core course exploring the legal and ethical issues emerging in the field of biotechnology. Advanced mathematics and computation figure prominently in the curriculum, which covers such current topics as genomic and proteomic biotechnology, microarray engineering, and structural biology. “One of the most beautiful aspects of this program,” says Simon Kasif, an ENG professor of biomedical engineering, “is that it’s producing a new breed of students capable of carrying out complex biological experiments and analyzing them with sophisticated computational ideas. In the past there were biologists who did pipetting and statisticians who did the analysis.”

The sequencing of the human genome was the “first event when all biologists understood that they could not survive without computers,” says Sandor Vajda, an ENG professor of biomedical engineering and one of the core bioinformatics faculty. “It is simply not possible to access all of this genomic information in any other way. You need excellent databases and very good interfaces for searching. As the computing speed goes up, we will be able to answer much more complex questions than we have in the past, going beyond simply searching the database.” The computing resources at Boston University—such as the Biowulf Linux Cluster, an IBM 128-node multiprocessor—facilitate the massive number of calculations that arise when manipulating gene sequences and protein structures. For more information about the Bioinformatics Graduate Program, see bioinfo.bu.edu.

Center for Advanced Genomic Technology (CAGT)

The nascent Center for Advanced Genomic Technology (whose acronym, CAGT, is a play on the four bases of DNA, cytosine, adenine, guanine, and thymine) comprises the research core of the bioinformatics program. Directed by DeLisi, it was founded in 2002 as a direct offshoot of the molecular engineering research laboratory (MERL), which DeLisi established in 1990 when he was dean of ENG. CAGT is divided into four laboratories exploring different aspects of genomics and proteomics, the study of the structure and function of the proteins that genes produce.

Biomolecular Systems Laboratory

The biomolecular systems laboratory (BSL), directed by DeLisi, is developing computational and experimental methods for monitoring changes in proteins and genes inside a cell as it responds to its environment. To this end, DeLisi’s group has been improving DNA microarrays, a technology now common in thousands of laboratories around the world. Often referred to as a DNA chip, a microarray is usually a piece of glass about the size of a microscope slide that is coated with a grid of thousands of spots of DNA. Each spot contains millions of copies of short DNA sequences, and a computer keeps track of what’s where. The beauty of the array is that it makes it possible to measure the activity of thousands of different genes at the same time.

“The problem,” DeLisi says, “is that the arrays currently don’t work very well, and more and more people are losing confidence in them. Probably 90 percent of what we see on an array is in error.” He and his colleagues have developed software to dramatically improve the accuracy of the microarrays.

BSL researchers are also developing high-throughput methods for identifying sets of proteins that are activated and deactivated as conditions change inside a cell. With assistance from BU’s Fraunhofer Center for Manufacturing Innovation, BSL is forming Boston Array Technology, a company that will produce a new kind of microarray for identifying thousands of proteins using only the genome sequence of the organism being studied.

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