Environmental Factor, December 2007, National Institute of Environmental Health Sciences
Summer Intern Presents at Bioinformatics Conference
By Eddy Ball
When Venus Welch came to NIEHS to work in the 2007 Summers of Discovery program, she had no idea that five months later she would be addressing experts in toxicogenomics and bioinformatics at the First International Conference on Toxicogenomics Integrated with Environmental Sciences (TIES). Held October 25 - 26 at North Carolina State University, TIES highlighted cutting-edge research that ties together the two disciplines in an effort to maximize the utility of alternative assessment methodologies.
The conference also featured four student presenters chosen as especially promising by their mentors. Welch was one of them, presenting a study titled "Microarray Gene Expression Reveals Biological Pathways Perturbed in 1, 2- and 1, 4- Dichlorobenzene Hepatotoxicity" and taking home an award of $200 for her performance.
Welch is a doctoral candidate in integrated biosciences with a focus in environmental toxicology and toxicogenomics at Tuskegee University. When she began her internship, she was well grounded in biology, but readily admitted that the world of bioinformatics was "way outside my comfort zone." Welch was fortunate enough to spend her summer of discovery under the mentorship of Pierre Bushel, Ph.D., NIEHS bioinformatics manager and a member of the TIES 2007 Organizing Committee (see story in Science Notebook) and to work with Molecular Pathology Group Guest Researcher Gary Boorman, Ph.D.
With Bushel's help, Welch spent the summer engaged in a crash course on microarray gene expression analysis and the principles of bioinformatics, completing the first drafts of the study she presented at TIES before she returned to Tuskegee for the fall semester. "Pierre was extraordinarily encouraging and patient," she recalled. "He helped me understand the basics of bioinformatics and how to apply it to research."
The TIES conference was her first experience making a presentation to senior colleagues as a graduate student, and Welch said she was intimidated by the thought of facing a roomful of experts from around the world, especially the statisticians in the audience.
As it turned out, Welch was amply prepared for the questions she was asked at the end of the talk. She presented her study a second time at the Southeast Regional Collegiate Environmental Science and Health Symposium sponsored by the Centers for Disease Control and Prevention November 14 in Atlanta and felt even more confident when she faced the audience there.
Welch plans to apply for the 2008 summer program and build on last summer's work in bioinformatics. She is now in the process of preparing a proposal to expand on her microarray studies for her dissertation.
Welch took away an important lesson from her experience at NIEHS, one that is sure to impact the direction of her professional life as a student, postdoctoral fellow and environmental sciences investigator. "The key thing I learned last summer with Pierre was the importance of accurate statistical and data analysis," she explained. "Without successful analysis, bench top research really can't be properly applied."
Utilizing Microarray Data in Liver Toxicity Studies
Venus Welch's study, "Microarray Gene Expression Reveals Biological Pathways Perturbed in 1, 2- and 1, 4- Dichlorobenzene [DCB] Hepatotoxicity," is the type of research investigators will be performing with compounds as toxicology studies increasingly take advantage of the marriage between omics methodologies and bioinformatics.
Welch's objective was to determine the differences in gene expression patterns and biological pathways between two isomers used in pesticides. 1, 2 DCB is used in potent herbicides, while a less harmful isomer, 1, 4, DCB, is found in mothballs and toilet deodorant blocks.
Welch analyzed the data from assays of the livers of male Fisher rats that received various levels of oral dosing of the two isomers. She also made clinical chemistry measurements of ALT and AST enzymes and histopathology observations of liver tissue.
Anchoring gene expression to sample phenotypes with end-point measurements, Welch determined the central regulating role of tumor necrosis factor and identified gene expression patterns related to apoptosis, MAP kinase signaling and metabolism in the liver. She also identified another key enzyme that is differentially expressed between the pathways of the isomers of DCB.
Building on this kind of information, toxicogenomics shows promise in using alternative testing methods to predict toxicity before apical endpoints are reached. Gene expression data may have useful applications in regulation of hazardous chemicals and in trauma medicine settings.