Our department is about ... Preparing for the future

PhD student Travis Cook (pictured above) receives funding from the Biostatistics, Epidemiologic, and Bioinformatic Training in Environmental Health, a training program directed by Professor Lianne Sheppard. Read the story about his research here.

“Big Picture” Technologies: A Systems Approach to Research

Theo Bammler (background), who manages the Bioinformatics and Biostatistics Facility, discusses
an assay using microarray technology with Fred Farin,
who directs the Functional Genomics Laboratory.
Photo: Elizabeth Sharpe

Technologies that can analyze and make sense of large swaths of data derived from the human genome can greatly advance environmental health research. They can provide the “big picture”—sweep over thousands of genes and identify particular ones affected by a chemical exposure, such as from pesticides. They can help researchers understand the biological impact of a specific environmental pollutant.

But these tools also require considerable resources and expertise. An array-based global transcriptome profiling study may cost between $10,000 and $30,000, and microarray processing instruments, which can analyze potential biological markers for disease, are well over $100,000 per unit. Individual scientists often do not have these kinds of resources.

For this reason, two centers affiliated with the department (the Center for Ecogenetics and Environmental Health and the Superfund Research Program) developed the technical infrastructure and the facilities—the Functional Genomics Laboratory and the Bioinformatics and Biostatistics Facility—to pair researchers with experienced staff who can help develop and implement studies that use these complicated but powerful assays and equipment. Both centers are funded by the National Institute of Environmental Health Sciences.

The Center for Ecogenetics and Environmental Health (CEEH), directed by Professor David Eaton, fosters collaborations among investigators from different disciplines to understand how genetic factors influence human susceptibility to environmental health risks. The Superfund Research Program, directed by Professor Harvey Checkoway, brings scientists together to uncover human and wildlife biological markers of exposure to and physiological damage from environmental toxicants.

A third center outside the department, the Center on Human Development and Disability, which is funded by federal legislation and the National Institute of Child Health and Human Development, uses services provided by the laboratory and facility for research on a broad spectrum of problems relevant to individuals with neurodevelopmental disabilities.

Early on, the Functional Genomics Laboratory performed genotyping assays for CEEH researchers. The studies compared base-pair sequences that make up an individual’s DNA. They were looking for DNA variations associated with susceptibility to an adverse outcome when exposed to a particular environmental toxin or pharmacologic agent. And the researchers discovered them, explained Fred Farin who directs the laboratory. With Research Professor Emeritus James Woods, the laboratory has identified DNA variants associated with neurobehavioral changes from mercury exposure. In addition, their collaborative studies with Professor Allan Rettie (School of Pharmacy) on warfarin, a blood- thinning medication used to prevent blood clots, heart attacks, and stroke, found that people who had a genetic variant are more prone to catastrophic bleeding events. These and subsequent findings influenced the US Food and Drug Administration’s decision in 2007 to require the drug label to state that genetic makeup affects a person’s response to the medication.

Fast forward to today. “It’s not enough to generate data,” said Theo Bammler. He manages the Bioinformatics and Biostatistics Facility, which applies computer programming and biostatistical algorithms to decipher and extract information gleaned from functional genomics-related technologies. Microarrays, for example, can display genetic fingerprints, simultaneously measuring the reaction or “expression” of thousands of different genes to a drug, an environmental pollutant, or a pathogen. The data output without bioinformatics tools is too great to meaningfully visualize. Imagine finding patterns in a spreadsheet crisscrossed by thousands of rows of discreet numbers.

In addition to researchers from the three centers, Farin and Bammler also find themselves approached by other UW investigators who would like to collaborate. The result: an impressive number of studies published in peer-reviewed journals, and in the last five years, they have coauthored more than 70 manuscripts.

One study was the first of its kind to find a potential biomarker for low-level, chronic exposure to a toxin found in some kinds of algae. Another study looked at the molecular impact of organophosphate pesticides and heavy metals like copper on the olfactory systems of freshwater fish. Still another project investigated the mechanisms involved in the seasonal changes in bird brains—whereby the number of brain cells increase in spring and decrease in autumn. Their findings may one day have important implications for human neurogenerative diseases, which are characterized by brain cell death. “If we can figure out how to make these cells proliferate, we may be able to find a therapeutic approach to treat these diseases,” said Farin.

Functional Genomics and Bioinformatics

New technologies help answer research questions about how environmental exposures can cause injury and disease. Functional genomics works to uncover the relationship between the double helix control tower and how it steers the body’s biological mechanisms. To analyze potential biological markers for disease, scientists use a gene chip or micro- array instrument to measure the reaction or “expression” of thousands of different genes to a drug, an environmental pollutant, or a pathogen. Bioinformatics tools—computer programming and biostatistical algorithms—decipher and extract information gleaned from functional genomics-related technologies. Illustration: Cathy Schwartz