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Following the trails of cells: NIH awards $38 million for research

Rick Horwitz and Tom Parsons By Fariss Samarrai

Cells move. Their movement helps embryos develop, fashioning organs and tissues. White blood cells chase bacteria and viruses, preventing people from getting sick. Cancer cells crawl, using the bloodstream to spread disease.

Cell movement is an essential process that underlies health and disease. Yet despite many years of intensive study, a good understanding of the mechanics of this important phenomenon has remained out of biologists’ grasp.

In an effort to “glue” together large groups of scientists across several disciplines from many universities, the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health, has awarded a $38 million five-year grant to a U.Va.-led consortium of cell researchers. This is the largest NIH grant in the Medical School’s history, and among the biggest awards NIGMS has ever given. Their mission is to investigate cell migration, the process by which cells move from one location to another, such as during wound healing and the spread of cancer. The work will provide essential information that may eventually lead to new therapies for a wide variety of diseases, from cancer to arthritis.

“NIH is providing extraordinary support for highly innovative research in a very exciting and promising area of cell biology,” said Alan F. “Rick” Horwitz, U.Va. professor of cell biology, who is leading the newly organized, multi-institutional Cell Migration Consortium. Horwitz and J. Thomas Parsons, chair of the U.Va. department of microbiology, have assembled a multi-disciplinary team of 30 researchers from 10 institutions, including Harvard University, the Massachusetts Institute of Technology, the Scripps Research Institute and Johns Hopkins University.

Cells migrate using an extension-movement-retraction approach much like the forward motion of a snail. It is a complex molecular process, but the cell is, in effect, laying out feelers, gripping solid ground, pulling forward and releasing its grip from behind.

“We’ve pulled together the very best people in their respective fields to collaborate on a big-picture, interdisciplinary basic science project that has the potential to change our understanding of how cells work,” Parsons said. “This collaborative initiative is designed to break down the institutional barriers that so often inhibit the flow of new scientific information.”

The consortium is made up of biologists, chemists, biophysicists, optical physicists, mathematical modelers, computer scientists and engineers who will tackle problems from several points of view. U.Va. members of the consortium, besides Horwitz and Parsons, include Donald Hunt, University Professor of Chemistry and Pathology, William Pearson, professor of biochemistry, and Jay Fox, professor of microbiology.

NIH is funding the project at about $7.6 million per year, starting with $8 million the first year. The grant will be administered at U.Va. and the funds will be distributed to consortium researchers.

“This grant offers a fantastic opportunity for the University to further enhance our research efforts in areas where we already have great strengths and leadership capabilities,” said Gene Block, U.Va. vice president and provost. “It also challenges us to develop a new model for the creation of large-scale, multi-university research communities across many disciplines.”

The idea for the Cell Migration Consortium began about five years ago when Horwitz and Parsons were attending a scientific conference in Colorado. At the time Horwitz was a professor at the University of Illinois.

“We were talking about the complexity of cell migration research and came to realize that the work couldn’t get done unless there was a large group of interdisciplinary researchers working together on the problems from several perspectives,” Parsons said. “We got the idea to pull people together for this, and we proposed the idea to NIH. It was a long process, and now, with this level of funding, we believe we can accomplish our research goals.”

“This is one of the most significant grants the Medical School has ever received,” said Robert M. Carey, dean of the School of Medicine. “The faculty group we’ve assembled in cell motility and adhesion is among the best in the world.”
“The glue grant will allow us to work together sharing our findings quickly and efficiently, keeping together the big picture view in this extremely important area of cell biology,” Horwitz said.

Cell migration is one of the least understood areas of cell biology, according to Parsons, who said scientists still don’t understand how cells move from one area in the body to another, such as in cancer metastasis. “Our interest is in understanding the mechanisms that direct and regulate cell movement. By increasing our knowledge in this area, researchers may eventually find ways to encourage cell migration for wound healing, or for stopping the migration of cancer.”

“Understanding the mechanism of how cell migration occurs is critical to our understanding of diseases like cancer, arthritis and osteoporosis, as well as wound repair, embryonic development and tissue engineering,” said Horwitz. “For example, most people who have cancer don’t die from primary tumors but from tumor spread — that’s a migration problem. And a significant number of congenital brain defects are migration problems.”

Using state-of-the-art Web and interactive video technologies, consortium researchers will share and discuss data as it’s gathered.

“We’ll be able to share real-time data and make immediate analyses,” Horwitz said.
The consortium Web site will be accessible to scientists everywhere, making possible the timely sharing of findings, ideas and information. Members of the consortium, along with other researchers in the field, will meet annually to share information and evaluate focus areas, subgroups also will meet regularly, and all members will participate in monthly videoconferencing.

A long-term goal of the consortium is to produce an interactive computer model of a migrating cell.

“This would have predictive value for researchers whose goal is to regulate migration as a part of a therapeutic strategy,” Horwitz said. “We want to be able to visualize the dynamics of cells walking. This may lead to the development of biomaterials that could facilitate the healing of wounds.

“We plan to make the work of the consortium as dynamic as the cell itself,” he added. “We will be constantly evaluating our work, looking for new directions, following leads, much the way a cell seeks and receives direction when it moves.”

Parsons points out that therapeutics may be a long way off and that the consortium’s focus is strictly on understanding the immensely complicated processes of cell migration.

“The consortium will be the research hub for the eventual therapeutic spokes,” he said.


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