Sandia LabNews

Microarray technology could help in disease diagnosis, prevention

Sandia/UNM collaborations may lead to new ways to diagnose, prevent illnesses using microarray technology

Collaborations between Sandia and the University of New Mexico (UNM) may lead to a greater understanding of genomics and ultimately to new ways to diagnose, treat, and prevent illnesses.

George Davidson (9200) and David Haaland (1812) have been working with UNM researchers on two different projects using several of the same microarray scanning and computing technologies.

One research endeavor — initially funded through an internal Sandia Laboratory Directed Research and Development (LDRD) award and followed by grants from the W.M. Keck Foundation and National Institutes of Health (NIH) — involves Sandia, the UNM Cancer Research and Treatment Center (CRTC), and UNM High Performance Computing Education and Research Center (HPCERC). Using Sandia-developed software and computing capabilities, they are evaluating thousands of genes from some of the 100,000 tissue samples from leukemia patients maintained at the CRTC.

Eventually, higher throughput in these studies will be achieved with new Sandia microarray scanning technology. The goal is to determine pathological gene expressions in these cancer cells. This information will be useful for assigning patients to different treatment protocols and may ultimately lead to the development of drugs specifically targeted to these cancers.

In the other project, Dave and George are collaborating with Maggie Werner-Washburne, a UNM biology professor, to improve microarray analysis techniques and the interpretation of data from microarray experiments. Focusing on yeast cells, the fundamental research is now promising to provide better understanding of how cells transition from a quiescent to a growing state, which is involved in wound responses, cancer, and germination of spores, and the complex response of cells to bioagents. This more applied research is contributing to enhanced instruments and sensors to combat bio-threats.

Werner-Washburne work

The work with Werner-Washburne came first, emerging from discussions while she was the program director for Microbial Genetics at the National Science Foundation (NSF) in Washington, D.C. She returned to UNM to help create and lead a group of like-minded researchers interested in exploiting the genomics revolution and helping New Mexico laboratories develop these technologies.

George and Werner-Washburne began developing strong ties between the biology department and Sandia, which included training students and building the required equipment. The work was partially funded by a three-year University Research LDRD grant that began in 1999.

The research had three objectives — the most important being the establishment of viable biotech research collaborations between the two institutions. The second goal was to enable local microarray experiments and to develop the methods and process controls necessary to achieve high-quality results. The third was to research the issues of gene expression of yeast cells in quiescence and during re-entry into the cell cycle.

"The collaborations between Sandia and UNM have been quite successful," George says. "Importantly, we jointly developed the ability to conduct and analyze microarray experiments using either commercial gene array membranes or arrays printed on glass slides at the UNM Biology Department."

However, it became apparent that the commercial scanners for reading these arrays could be greatly improved, which led to David Haaland’s involvement.

"Maggie and I talked about our research when we would run into each other in our neighborhood park. At the time Maggie was working with microarray technology using two fluorescent dyes to study gene expression of yeast cells, and I was doing hyperspectral imaging in the infrared," David says. "It became apparent that the hyperspectral imaging could be useful in Maggie’s efforts."

Werner-Washburne says that the Sandia collaborations started during their walks in the park have been particularly rewarding.

"As a result of our Sandia collaborations, we have been able to take a systems approach to this problem," she says. "There are very few laboratories in the country that effectively incorporate biologists, computer scientists, chemists, mathematicians, and engineers at this level. It is the future of genomics, and we have a unique opportunity to make important contributions and have fun at the same time."

W.M. Keck Foundation

About a year into the Sandia/Werner-Washburne project, the W.M. Keck Foundation of California awarded the UNM Health Sciences Center, which has the largest leukemia tissue repository in the world, and Sandia a $1 million grant to apply microarray research to leukemia.

George says that the "attractive part of the proposal was the combination of high-performance computing capability and instrumentation technologies at Sandia with the unique tissue repositories at UNM."

This potent combination is directed toward learning what causes the cancer and which drugs and therapies might be tailored to each individual patient for optimal treatment.

"It is our hope for the future that such studies will allow us to develop specific and more effective therapies targeted to each individual patient," says Cheryl Willman, CRTC director and principal investigator of the Keck grant.

Of the $1 million, UNM received 70 percent, and George and David share 30 percent. The CRTC handles all clinical interactions and the laboratory preparations, including scanning the slides with commercial equipment. Those data are then analyzed using new methods developed by George, David, Shawn Martin (9212), and the computer scientists from the HPCERC. David is also developing a powerful hyperspectral imaging scanning device that will greatly improve on the commercial scanner now in use.

VP1000 Al Romig says the collaborative work between UNM and Sandia is an example of a scientific win-win situation.

"Sandia’s high throughput methodology, from the microarray scanners to the mathematical tools for data extraction, will have a major impact on a variety of bioscience and technology studies, from basic research of disease to mitigating the biothreat from emergent diseases and terrorism," Al says. "It’s simply another example of Sandia’s expertise in physical science, engineering, and computing applied to biological problems. It represents a true scientific win-win. There are problems that are intractable with traditional tools of bioscience, yet attacking them allows Sandia to nurture its own competencies to the benefit of all of our national security problems."