Collaborative Cross To Provide Powerful Resource For Mouse Model Researchers Worldwide

The project, dubbed the CollaborativeCross, has officially begun with a $1.25 million grant over five yearsfrom the Ellison Medical Foundation. When completed in about sevenyears, researchers worldwide will be able to fully exploit the geneticpower of the mouse. Each of the estimated 1,000 strains derived fromthe carefully selected original eight breeds represents a resource thatcan be used repeatedly to accumulate data.

"Ultimately, thiseffort will allow us to do a much better job of modeling humanpopulations and diseases because we will have 1,000 lines of mice thatcarry the kinds of genetic diversity representative of people," saidDabney Johnson, a genetics researcher in ORNL's Life Sciences Division.Johnson headed a team that wrote the proposal to the Ellison MedicalFoundation.

At the heart of the project is the new $14 millionLaboratory for Comparative Functional Genomics at the Department ofEnergy's ORNL. The pathogen-free 36,000-square-foot facility completedin 2004 boasts accommodations for 80,000 mice, cryogenic storage andother state-of-the-art features. It is at this designated DOE userfacility that the breeding of the eight strains taken from around theworld will be performed to initiate up to 1,500 strains of mice. Ofthose, researchers expect about 1,000 strains to be viable asinbreeding proceeds.

Without DOE's stewardship of the new mousefacility, the project would not be possible, said Johnson, who notedthat DOE is contributing not only the space within the facility butalso the technical capabilities that will allow the work to beperformed.

The project, which will occupy about half of the newORNL mouse house's capacity, is a perfect fit for ORNL, according toJohnson. "Projects like this are a big part of why the Department ofEnergy built this facility. We now have the building and the resourcesto host a project with potentially vast benefits to people around theworld," she said.

Several universities and institutions,including The Jackson Laboratory, the University of Tennessee and theUniversity of North Carolina, are participating in the effort, whichJohnson hopes continues to gain momentum over the next several months.Already, researchers around the world have expressed significantinterest and Jackson Lab has provided the parental strains of mice.

Theproject represents a significant departure from previous approaches andresearchers say is necessary to take the next step in developing acommunity resource for understanding the genetic and environmentalcomplexity of human diseases.

"For the last 30 years it has beenall right to study one gene at a time, but we realize that we've goneas far as we can with that approach," Johnson said. "So this is theonly way to accomplish what we're setting out to do now. When we'redone, we will have reduced genome sections to small enough pieces thatonly one to five genes are possible candidates to control a specifictrait."

Controlling environmental variables will play a huge rolein enabling researchers to identify and potentially diagnose and treatan assortment of chronic human conditions, including cancer, pulmonaryand cardiovascular diseases, obesity, diabetes, behavioral disordersand neurodegenerative diseases.

Another component of the projectwill be exposure biology, which ultimately attempts to explain why somepeople are more susceptible to toxins or other insults than others.Johnson also expects the Collaborative Cross to attract guestresearchers who will be provided with laboratory space to work onspecial projects that have been approved by an external review board.The four-member board consists of renowned researchers from CaseWestern Reserve University, The Jackson Laboratory, Lawrence LivermoreNational Laboratory and Battelle Memorial Institute.

Johnson alsonoted that the project will generate large amounts of data and enablepredictive modeling and simulation that will require the resourcesprovided by ORNL's supercomputer. In 2004, ORNL was selected as thesite for DOE's National Leadership Computing Facility, which with 50teraflops of sustained capacity and a capacity of 250 peak teraflopswill be the world's most powerful supercomputer for research.

ORNLis managed by UT-Battelle for the Department of Energy. Funding for themouse facility is provided by DOE's Office of Biological andEnvironmental Research within the Office of Science. The EllisonMedical Foundation supports basic biomedical research on aging relevantto understanding aging processes and age-related diseases anddisabilities.