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GEMS Showcases Systems Biology Approach at Spring Meeting

By Eddy Ball
May 2007

Spring 2007 GEMS Meeting
Attendees at the Spring 2007 GEMS Meeting enjoyed lunch before the presentations began. (Photo courtesy of Steve McCaw)

Van Houten
Van Houten was the keynote speaker at the meeting. (Photo courtesy of Steve McCaw)

Greg Stuart, and Chris Portier
When GEMS President Greg Stuart presented Portier with his honorary coffee mug, Portier joked that he'd need to list it on his annual NIEHS financial disclosure statement. (Photo courtesy of Steve McCaw)

Professor Kaufmann
A systems biology approach helped UNC Professor Kaufmann pinpoint where in the cell cycle that double strand breaks in DNA were more likely to evade DNA repair. (Photo courtesy of Steve McCaw)

unnamed man, giving a presentation
A major research interest in the Magwene Lab at Duke is developing analytical and algorithmic approaches for addressing problems in systems biology and evolutionary biology. (Photo courtesy of Steve McCaw)

The Genetics and Environmental Mutagenesis Society (GEMS) held its 2007 Spring Meeting April 16th at the Environmental Protection Agency (EPA) RTP headquarters. The meeting's theme was "Integrative Bioinformatics: Systems Biology Approaches to Genetics, Metabolism and Disease." In the absence of GEMS President-Elect Rose Anne McGee, President Greg Stuart, Ph.D., chaired the meeting.

Speaking at the half-day event were two NIEHS investigators, Ben Van Houten, Ph.D., and Chris Portier, Ph.D., and two Triangle-area biologists, William K. Kaufmann, Ph.D., of the University of North Carolina at Chapel Hill and Paul M. Magwene, Ph.D., of Duke University. A fifth speaker, Michael B. Yaffe, Ph.D., of Massachusetts Institute of Technology, was unable to attend the meeting due to flight cancellations in Boston.

The meeting opened with an introduction to the systems biology approach by Van Houten, who is a senior investigator and head of the DNA Repair and Mitochondrial Damage Group in the Laboratory of Molecular Genetics (LMG). Van Houten explained the difference between the characteristic reductionist approach in science and the emphasis on synthesis and integration that is the hallmark of systems biology.

"Systems biology is a complete description of how all of the components of a biological system work together," Van Houten explained as he outlined the four basic steps of the approach. After describing the system as completely as possible, he continued, "then do something to that system, add a chemical, knock out a gene, perturb it in some way."

With the system perturbed, the researcher then measures the changes in that system as globally as possible - typically using "omics" methodologies and taking advantages of databases, such as genome sequencing, RNAi libraries and mapping. Based on insight into the system gained by studying it under stress, he noted, "you can then describe the system much better because you understand how the system changes."

Van Houten then demonstrated how a systems biology approached helped his group gain insight into accumulated mitochondrial DNA damage and common gene expression patterns unique to the pathogenesis of disease in patients with Friedreich's Ataxia. Pathways analysis allowed the team to identify transcriptional changes associated with cell death, cardiovascular disease, neurological disease, and muscular and skeletal disorders.

In his presentation, Portier, NIEHS associate director and director of the Office of Risk Assessment Research, focused on applying the tools and principles of systems biology to evaluation of health risks from exposure to environmental agents. This kind of research can have important regulatory consequences, and researchers must take into consideration such factors as economic cost and society's wants in an effort to formulate policies based on rigorous scientific investigation and sophisticated computer modeling.

Kaufmann, a researcher in the UNC Laboratory of Human DNA Metabolism, has applied systems biology to his investigations into the severe chromosomal instability that leads to development of malignant melanoma. He and his colleagues have used computational tools to create models of nucleotide excision repair and the G2 checkpoint. With these models they have simulated the cell's response to DNA damage in order to discover new alleles that can protect against the ultra violet light-induced chromosomal damage that triggers this environmental cancer.

Closing out the program, Magwene, a professor of biology at Duke Institute for Genome Sciences and Policy, discussed the experimental and computational approaches his group has used in yeast to understand the phenomenon of pleiotrophy, the ability of a gene to manifest itself in more than one way in different tissues. Magwene has taken a systems approach to explore the contributions of genetic architecture, genetic variation and evolutionary history to producing these effects.

To find out more about upcoming programs sponsored by GEMS or to join the group, visit the GEMS website(http://gems-nc.org/index.html Exit NIEHS. GEMS actively promotes the involvement of students by offering memberships for $5.00 and a reduced fee of $10.00 for meeting registration and encourages participation by minority groups, women in science, and handicapped or other historically under-represented groups, according to Stuart.

NIEHS and GEMS

Celebrating its twenty-fifth anniversary this year, GEMS is a regionally active group of scientists, toxicologists and others sharing a common interest in the interplay of genetics and the environment. The group holds two meetings each year, one in April and a larger, full-day event in November that features talks and poster session competitions for postdoctoral fellows.

Although the GEMS membership includes scientists with an interest in toxicology and mutagenesis from many of the Triangle's government agencies, universities and private sector research groups, NIEHS scientists and fellows make up a significant part of the membership and board of directors:

President Greg Stuart, Ph.D. - Stuart works as a special volunteer in the Mitochondrial Replication Group with LMG Director William Copeland, Ph.D. He is supported by a National Research Council Research Associateship Award from the National Academies.

President-Elect Rose Anne McGee - McGee is a biologist working in the Division of Extramural Research and Training. She is an associate scientific review administrator with the Scientific Review Branch.

Secretary Gloria Jahnke, D.V.M. - Jahnke is a toxicologist employed by Sciences International who, until recently, worked as a contract scientist with the National Toxicology Program at NIEHS.

2005-2007 Councilor Janice Allen, Ph.D. - Allen is a molecular biologist working in the Division of Extramural Research and Training. She is a health scientist administrator in the Scientific Review Branch.

2006-2008 Councilor Cindy Innes - Innes is a biologist with the Environmental Toxicology Program. She is involved in research in the Laboratory of Molecular Toxicology.

2007-2009 Councilor Dan Shaughnessy, Ph.D. - Shaughnessy holds a doctoral degree in environmental health. He was a fellow in the Laboratory of Molecular Carcinogenesis before taking a position as a health program administrator in the Division of Extramural Research and Training Susceptibility and Population Health Branch.

2007-2009 Councilor Kristine L. Witt - Witt is a toxicologist in the Environmental Toxicology Program. She is involved with research in the Toxicology Operations Branch.

PostDoctoral Member Dario C. Ramirez, Ph.D. - Ramirez is a fellow in the Environmental Toxicology Program and works in the Laboratory of Pharmacology and Chemistry. When he won the Best Talk/Travel Award at the 2006 GEMS Fall Meeting, he was invited to join the board.



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