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Seattle firm's genomics analysis software affords Washington State University researchers look at molecular changes in young, growing hearts
Major heart journal article finds that titin, largest protein in body, is biggest in the tiniest patients
PULLMAN, WA - January 24, 2004 - Washington State University researchers using the GeneSifter data analysis system have made great strides studying heart development as published in the journal Circulation Research. Dr. Sunshine Lahmers, a cardiologist working in the Granzier-Labeit laboratory in WSU's Department of Veterinary Clinical Sciences, is using GeneSifter in a unique way to study the role of titin, the largest protein in the human body, in normal heart development and its possible relationship to heart disease.
Titin is a giant, spring-like protein that helps give all muscle its elastic recoil, and the heart its ability to retain its shape after each beat. The body contains a lot of it: titin is the third most abundant muscle protein, and there is nearly a pound of it in the heart and other muscles. But sheer size and abundance aren't why Lahmers' research is so interesting.
There are multiple forms of titin, formed by different combinations of "exons," or sections of the titin gene, whose protein products are linked together like the cars of the titin train. Lahmers' work, described in a March article in Circulation Research, has revealed that an "unusually large" form of titin in the hearts of nearly-born and newborn children makes their growing hearts more elastic. In the first few months after birth, this "fetal cardiac titin" is replaced by smaller and stiffer forms of titin.
According to Lahmers, these changes are necessary to accommodate the dramatic alterations in a newborn's body that occur during birth, such as the transition from living in the womb to breathing air.
Computer software is one of the most important tools of 21st century life scientists. Lahmers credits GeneSifter, a data analysis system from Seattle-based VizX labs, with providing the flexible and highly sophisticated software platform she needed for her complex research. Lahmers and her colleagues performed complex laboratory experiments using splice-variant microarrays, generating massive amounts of data.
Dr. Lahmers' work is a collaboration between veterinary and medical doctors to understand species differences and similarities in heart development and disease. The work evaluated a wide range of species, giving researchers a fuller picture of how titin behaves in the heart of young animals and children, and further increasing the amount of data. GeneSifter helped Lahmers and her colleagues analyze that immense amount of data quickly and accurately, cutting the time spent on data analysis from months to hours.
"GeneSifter helped the routine number crunching go very quickly," Lahmers said, "and that gave me more time to focus on the biology behind those numbers."
GeneSifter also helped Lahmers work with some unique aspects of her research that other software could not. "The data I was using was in a unique form, but GeneSifter was flexible enough to load it without much problem. Likewise, the system was flexible enough that they could add specific options to the system that I could use.
"Typically, researchers want to know how much a gene is expressed compared to all other genes," Lahmers explained, "but I was specifically interested in how often one form of the titin gene was expressed compared to the most common form. GeneSifter's science staff made that possible."
"Dr. Lahmers' research used splice-variant microarrays in a unique way," noted Dr. Christian Wade, VizX Labs staff scientist. "And when we identify a unique type of research, GeneSifter's Web-based flexibility allows us to add features and adjustments to that make that research easier. Other researchers can then access them too, since it's all Web-based."
VizX has been collaborating with Lahmers since 2002, when the company first approached the lab after learning of her novel software needs. The GeneSifter scientific team reviewed her data and optimized the GeneSifter system for its analysis.
VizX Labs Director of Science, Dr. Eric Olson, said he was gratified that GeneSifter has been useful to Lahmers. "The research is interesting, because of the size and unique nature of the titin molecule; it is innovative, because of how she is using microarrays; and it is important, because of the clinical potential to save lives. I am pleased that GeneSifter contributes to such solid science, in this case and in many others."
About GeneSifter
GeneSifter is the accessible, Web-based microarray data analysis system for research scientists, which is now available from VWR International both as a stand-alone product and bundled with IBM computers as a part of the In Silico program. GeneSifter helps researchers understand the biology™ underlying gene expression patterns as it helps them determine the statistical and biological significance of their data. Customer comments are available online at www.genesifter.net/product-info_testimonials.php. Downloadable graphics, including screenshots of the GeneSifter Lab Edition and the new GeneSifter Core Edition, may be viewed online at www.vizxlabs.com/downloadable_images.html.
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Washington State University researchers are tackling more than just titin. Scientists at WSU, ranked as one of the top 50 research universities in the country, are doing research into biological mysteries that could lead to everything from better defenses against bioterrorism to male contraceptives, with quite a bit in between. In 2003, WSU faculty led over $242 million in research across a wide range of disciplines.
Dr. Derek McLean of the animal sciences department is leading research into the molecules made during sperm production in mice, rats and cattle. Like Lahmers, McLean's group is doing most of their research using microarrays. The ultimate goals of this project are to find possible avenues for male contraceptives, identify genes that can cause reproductive failure, and to design strategies to increase reproductive efficiency in cattle.
Dr. Guy Palmer, a professor of microbiology and pathology, is doing research into ways to develop new vaccines for both animals and humans, and to improve the safety and efficiency of current vaccines, including diseases that could be used for bioterrorism.
Microarrays are one of the most powerful tools scientists have when trying to determine the actions of genes.
A microarray contains thousands of spots in an ordered grid on a microchip about the size of a stamp. Each of these spots is tiny-smaller than the period at the end of this sentence-and a single microarray can contain spots for tens of thousands of genes.
Each single strand in this collection will find its partner from a group of active genes, which have been extracted from the cells being studied. The single-stranded gene fragments are labeled with fluorescent tags to tell the researcher which ones have found their partners. They are imaged, and the color and brightness of each spot is measured. Brighter spots indicate higher gene activity.
The researcher must then sift through a huge amount of data to determine if a gene has become activated or not, and to compare patterns between different groups of cells. When dealing with such massive amounts of data, specialized software such as GeneSifter is required.
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