Exploring the Next Phase of the Human Genome Investigation

Using some poetic license, you could consider the human genome as the dramatic script of each life. Its cast of star performers was recently supplied by the Human Genome Project; researchers in that effort identified each protein-encoding gene in the genome. Naming the supporting cast, however, has only just begun. This time, the playwrights will be scientists working on the National Human Genome Research Institute’s (NHGRI’s) new ENCODE project.

Among the 14 principal investigators in this leading-edge project is Zhiping Weng, an assistant professor of biomedical engineering in the Boston University College of Engineering. Together with co-investigators Chumning Ding, research assistant professor in Boston University’s Center for Advanced Biotechnology (CAB), and Charles Cantor, a professor of biomedical engineering and director of CAB, Weng has received from NHGRI a three-year grant totaling $1.5 million.

For their study, Weng and her colleagues will work to develop and improve new and existing technologies for determining the role of genetic material that does not contain instructions for proteins. Weng will concentrate on describing how particular elements, associated with what are known as promoter regions, act individually and collaboratively to regulate protein-encoding genes. By characterizing the role these elements, called cis-elements, have in transcriptional regulation, Weng and colleagues will spotlight how genetic “ensemble performances” determine everything from disease development to tissue function.

The ENCODE project is an international consortium of scientists from government, industry, and academia. ENCODE, or encyclopedia of DNA elements, picks up the search for understanding the human genome where the Human Genome Project left off. It focuses on all the biologically active elements in the roughly 98 percent of the genome that does not code for proteins, the genome’s so-called functional elements.

Although protein-coding genes are usually front-and-center in investigations of DNA, the ENCODE endeavor addresses the fact that a huge amount of the biological activity associated with the transcription of protein-encoding genes is, in fact, directed by functional elements, like the cis-elements being investigated by Weng’s team.

In a divide-and-conquer approach, ENCODE researchers will bring their individual investigations to bear on a particular one percent of the genome selected by ENCODE coordinators. Investigations will be divvied into two specializations: the study of large-scale existing technologies and the development of new or improved technologies for finding functional elements. Weng’s group will pursue the latter.

Weng’s team will use a battery of in-house computational algorithms to carefully characterize the starting points or “starts” of all the genes in the genome segment selected for the ENCODE project. They also will derive the promoters for these genes. Promoters, which are regions of the genome near the starts of the genes, contain high concentrations of cis-elements that are bound by regulatory proteins. These regulatory proteins can trigger or suppress gene expression and, thus, protein production.

Because many genes have multiple starts, Weng’s project will investigate the multiplicity of regulation, looking at what its effects may be on different disease conditions or on gene expression patterns in different types of cells; for example, liver cells and brain cells may be regulated to produce a particular protein but in different quantities. The team will develop algorithms that can predict how cis-elements influence the expression patterns of specific types of cells.

A novel aspect of Weng’s project is its combination of computational analysis with experimental testing. After computational analyses, Weng’s team will hone in on 40 genes for in-depth experimentation. This will include placing the genes in cells from different types of human tissue; growing those cells in the laboratory; and then, using a high-throughput, real-time technique developed by her collaborators Ding and Cantor, testing the genes to determine how the regulatory elements they carry control their expression patterns.

Cross-species comparison studies are an important, and somewhat unusual, aspect of the ENCODE project. By comparing the genomic sequences from human and other organisms, Weng will computationally identify portions of the human genome that are relatively similar to those in other organisms. These “conserved” regions are likely to harbor functional elements, since they have remained intact throughout eons of evolutionary selection. Weng will develop algorithms that incorporate cross-species comparisons in her search for regulatory elements.

“Using computational methods, it is easy to analyze a large number of genes and make predictions about the way they are regulated,” says Weng. “This project allows us to test those predictions with experiments. It also lets us collaborate with the other ENCODE laboratories, sharing our data to get the answers. This is really a project in which the whole is far greater that the sum of its parts.”

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Order of the Engineer Ceremony

More than 150 engineering undergraduates at the Boston University College of Engineering were recently inducted into the Order of the Engineer.

Founded in 1970, the Order “was initiated in the United States to foster a spirit of pride and responsibility in the engineering profession, to bridge the gap between training and experience, and to present to the public a visible symbol identifying the engineer.” Those who accept the obligation share the principle that public service is the primary purpose of engineering.

Seniors at the College of Engineering at Boston University formally accepted the Obligation of an Engineer during a ceremony in February. As a part of the induction ceremony, each student pledged that as an engineer, he or she would promise to “practice integrity and fair dealing, tolerance and respect, and to uphold devotion to the standards and dignity of the profession…. When needed, my skill and knowledge shall be given without reservation for the public good.”

As a reminder of this oath, each student accepting the obligation received a stainless-steel ring to be worn on the fifth finger of his or her working hand.

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Boston University College of Engineering students at the Order of the Engineer Ceremony in February.


Professor Theo de Winter congratulates Katie Lockwood, a senior in Manufacturing Engineering, as she accepts the "Obligation of an Engineer."

Alumni Wine Tasting

More than 30 ENG alumni gathered on Cape Cod in September for a wine tasting. The event was graciously hosted by Nick Lippis (ENG’84) and Lillian Lippis at their beautiful sea-side home in Chatham, MA. Dellie Rex, an associate professor with the Boston University School of Hospitality, was on hand to explain the finer points of wine and wine tasting.

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Incredible, Edible Car Design Contest

The Society of Manufacturing Engineers (SME), a student professional organization at ENG, hosted an Incredible, Edible Car Design Contest on Friday, September 26, 2003. The students were asked to design and construct a car made entirely of edible materials that would travel down a ramp in the shortest amount of time possible and continue as far as possible beyond the bottom of the ramp. All cars and their parts had to be edible, with all parts dry by the time of the competition to prevent residue being left on the track—in other words, zero emissions. Manufacturing engineering alumni (bottom, right) Lynn Worthy (ENG’01), Rolando Esquivel (ENG’88), and Lisa Lam (ENG’97) helped out as volunteer judges.

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Alumni Panel: Climbing the Corporate Ladder

A panel of alumni, 10 or more years in the working world, gathered at BU on October 30, 2003 and shared their work experience with current engineering students. The panelists discussed their personal strategies in “climbing up the corporate ladder” and the career paths that led them to their current positions.

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