STORAGE

A thousand new strains of mice being bred at Oak Ridge National Laboratory as part of an international effort will provide researchers with a powerful resource for studying human disease. The project, dubbed the Collaborative Cross, has officially begun with a $1.25 million grant over five years from the Ellison Medical Foundation. When completed in about seven years, researchers worldwide will be able to fully exploit the genetic power of the mouse. Each of the estimated 1,000 strains derived from the carefully selected original eight breeds represents a resource that can be used repeatedly to accumulate data. "Ultimately, this effort will allow us to do a much better job of modeling human populations and diseases because we will have 1,000 lines of mice that carry the kinds of genetic diversity representative of people," said Dabney Johnson, a genetics researcher in ORNL's Life Sciences Division. Johnson headed a team that wrote the proposal to the Ellison Medical Foundation. At the heart of the project is the new $14 million Laboratory for Comparative Functional Genomics at the Department of Energy's ORNL. The pathogen-free 36,000-square-foot facility completed in 2004 boasts accommodations for 80,000 mice, cryogenic storage and other state-of-the-art features. It is at this designated DOE user facility that the breeding of the eight strains taken from around the world will be performed to initiate up to 1,500 strains of mice. Of those, researchers expect about 1,000 strains to be viable as inbreeding proceeds. Without DOE's stewardship of the new mouse facility, the project would not be possible, said Johnson, who noted that DOE is contributing not only the space within the facility but also the technical capabilities that will allow the work to be performed. The project, which will occupy about half of the new ORNL mouse house's capacity, is a perfect fit for ORNL, according to Johnson. "Projects like this are a big part of why the Department of Energy built this facility. We now have the building and the resources to host a project with potentially vast benefits to people around the world," she said. Several universities and institutions, including The Jackson Laboratory, the University of Tennessee and the University of North Carolina, are participating in the effort, which Johnson hopes continues to gain momentum over the next several months. Already, researchers around the world have expressed significant interest and Jackson Lab has provided the parental strains of mice. The project represents a significant departure from previous approaches and researchers say is necessary to take the next step in developing a community resource for understanding the genetic and environmental complexity of human diseases. "For the last 30 years it has been all right to study one gene at a time, but we realize that we've gone as far as we can with that approach," Johnson said. "So this is the only way to accomplish what we're setting out to do now. When we're done, we will have reduced genome sections to small enough pieces that only one to five genes are possible candidates to control a specific trait." Controlling environmental variables will play a huge role in enabling researchers to identify and potentially diagnose and treat an assortment of chronic human conditions, including cancer, pulmonary and cardiovascular diseases, obesity, diabetes, behavioral disorders and neurodegenerative diseases. Another component of the project will be exposure biology, which ultimately attempts to explain why some people are more susceptible to toxins or other insults than others. Johnson also expects the Collaborative Cross to attract guest researchers who will be provided with laboratory space to work on special projects that have been approved by an external review board. The four-member board consists of renowned researchers from Case Western Reserve University, The Jackson Laboratory, Lawrence Livermore National Laboratory and Battelle Memorial Institute. Johnson also noted that the project will generate large amounts of data and enable predictive modeling and simulation that will require the resources provided by ORNL's supercomputer. In 2004, ORNL was selected as the site for DOE's National Leadership Computing Facility, which with 50 teraflops of sustained capacity and a capacity of 250 peak teraflops will be the world's most powerful supercomputer for research.