A research team at the UConn Health Center has recently been awarded a $4 million federal grant to develop "The Virtual Cell," a computer system that will simulate cell behavior.

The grant, received from the National Institutes of Health, helps underwrite development of a computer system that will allow scientists to model the inner workings of cells: from producing energy, to performing their specialized tasks, to replication, growing old and expiring.

The Virtual Cell is intended to simulate on the computer screen what happens in a real cell. Add a stimulus and the program will reflect how a cell would respond. Considering the nearly infinite number of stimuli, a cell's varying reaction to them and the numbers and types of cells that exist, the complexity of the project immediately becomes clear.

"This is an enormous undertaking," says Leslie Loew, professor of physiology and director of the Center for Biomedical Imaging Technology (CBIT), who heads the team, "but we're very excited about it."

Like the human genome project, a multi-billion dollar, 15-year effort to discover all 60,000 to 80,000 human genes, the creation and development of a comprehensive framework for understanding cell biology is a long-term and expensive project. Loew says the cell project could take 15 or 20 years or more.

He says the project began four years ago, when John Carson, a professor of biochemistry, asked Jim Schaff '91, a computer engineer and graduate of the School of Engineering, if it would be possible to visualize deformations in the surface of a cell by applying the laws of physics to three-dimensional digital images. Schaff produced the first model, "a cell whose membrane you could poke and pull with a computer mouse," says Loew.

"After four years of work, we know we've just scratched the surface," he says. "But this will be the natural next step after the genome project tells us about the identities of all the genes and proteins. Now we have to figure out how they all work together to make cells do what they do."

The project requires cooperation from several disciplines: Besides Loew, who is trained in chemistry and biophysics, the team includes computer scientists, a mathematician, microscopists, molecular biologists, cell biologists, and a physicist specializing in numerical methods.

The Virtual Cell program will be easy to use, accessible, fast and economical. It is expected to improve productivity and save time and money by allowing scientists to more efficiently design experiments on cells. Scientists with hypotheses could refine their ideas on The Virtual Cell program before taking the experiment to the next stop: the laboratory.

To access The Virtual Cell, authorized scientists will need only to call up an Internet site using a web browser like Netscape or Explorer, and follow the directions posted there.

The program will be beneficial to cell biologists, drug designers, and neuroscientists. It will also be a valuable teaching resource. In general, scientists will be able to use the program to better understand the complex biological behavior of cells. For example, drug manufacturers could use it to test rationally and more economically the efficacies of various compounds on the functions of cells; it may be used to answer how neurons "learn" in response to repeated electrical inputs; geneticists could use The Virtual Cell to learn why gene defects can stop a cell from functioning properly; and students will be able to use it to see what cells do and learn about cell structure.

The team does not intend to sit down and write a computer program that predicts everything a cell does. There are too many variables contributing to too many outcomes for that approach to be feasible. Instead, the team is starting by developing a program that allows biologists to model limited events that are now known to take place within a cell.

The three areas of cell activity Loew and the team are now working on include: what occurs when a calcium wave passes through a neuron? what mechanisms cause a heart muscle cell to contract? and how does a glial cell - the cell that makes the myelin sheath that encases nerves - before replicating, send messages from its central nucleus to its edges?

These cellular functions have the advantage of being understood and finite. They can be seen and observed through microscopes or other visualizing devices, and they can be confirmed through experimentation. So these provide a good testbed upon which The Virtual Cell will be built.

"You don't have to know everything there is to know about muscle cells to ask questions about how muscle cells contract," Loew said. "Confining our models to limited, well defined questions gives us a starting point for the project. Without an incremental strategy, the project would be too complex to manage," he said.

As new knowledge is uncovered, those new insights can be programmed in to revise the existing virtual cell framework. Project team members are already revising some initial programming in a process Loew calls "continuous redesign."

In addition to the $4 million underwriting money, the NIH grant confers upon Loew's CBIT the designation National Biomedical Technology Resource. The designation means the lab, one of 60 such resources around the country developing state-of-the-art technologies in various fields - and the only one in Connecticut, will serve as a research center and clearing house for scientists needing data on cells and biological mechanisms.

Patrick Keefe