Two University scientists get DOD grants to further cellular investigations

Two University scientists, Terry Vanden Hoek and Milan Mrksich, have received grants of approximately $1 million a year for three years from the U.S. Department of Defense.

Two additional years of funding will be possible. The awards, part of the Multidisciplinary University Research Initiative Program, support research themes that are considered vital to national defense.

Vanden Hoek, an Associate Professor in Clinical Medicine, will work with colleagues at Argonne National Laboratory and the University of Michigan to develop tests that can quickly gauge the severity of injuries caused by rapid blood loss. These tests will help the military determine the best course of treatment for patients suffering massive blood loss. They may also help doctors treat civilian patients involved in accidents or even those who have had a cardiac arrest.

Doctors currently rely on crude measures such as blood pressure, pulse, breathing rate and temperature to determine whether a patient who has lost large quantities of blood will survive. Vanden Hoek’s team suspects that an additional useful measure may be the response by mitochondria, small cellular structures that convert fuel into energy.

The mitochondria “may provide an early warning signal, like the canary in the coal mine,” Vanden Hoek said. Mitochondria are very sensitive to the lack of oxygen. “We think that in the absence of oxygen there are rapid changes in the aggregation of various proteins within mitochondria,” he said.

Some mitochondrial changes might indicate mild to moderate cellular damage, a sign that damage is limited and the patient might recover. But others are more troubling. “There are certain clusters that appear to be a very bad sign,” Vanden Hoek said. “They’re almost like the ‘death committee.’ Once they have met, there’s no turning back.”

Mitochondria could be collected easily, even in a battlefield setting, by a quick swab to gather cells from inside the mouth. The researchers hope to develop a rapid assay that could determine whether the mitochondrial “death committees” had met. They also will seek new treatments that could affect how these mitochondrial protein clusters interact and thereby reverse the dying process.

This research may also provide a better understanding of the body’s response to sudden loss of the blood supply and could even suggest ways to protect tissues at risk, Vanden Hoek said.

Mrksich, a Professor in Chemistry and the College, will attempt to develop microelectronic devices that integrate cells as working components in collaboration with scientists and engineers from the California Institute of Technology, Johns Hopkins University, Northwestern University and the University of California, Santa Barbara.

The challenge is to find ways to link cells to electronic devices. “These are two different worlds of technology,” Mrksich said. But there are advantages to finding ways to bring the two worlds together.

“Cells offer the benefit that they carry out many functions that are still difficult to engineer,” he said. These functions might include the ability to serve as sensors of bio-warfare agents, to act as components in computational networks, to synthesize proteins for biological assays in lab-on-a-chip applications, and to automatically change pigmentation in a system of active camouflage.

“I personally think that the cell-based sensors will be the most likely application that derives from the work,” Mrksich said. Unlike their mechanical counterparts, cell-based sensors would be able to react to unanticipated or previously unknown biohazards.

For lab-on-a-chip applications, Mrksich and his colleagues hope to take advantage of the ability of the cell to make thousands of proteins. “The idea is that if you have a lab-on-a-chip system, instead of pre-making large numbers of proteins that are needed in biological assays, for example, it might be possible instead to put a cell in place and then instruct a cell to make the protein that is needed at any time,” Mrksich said.

Even more challenging ideas would be to use cells as components in computational networks, or even to develop a type of camouflage that instantly reacts to its surroundings.

Neural tissue in the brain is the inspiration for using cells to perform computation, although the concept remains unproven. The skin of an octopus inspired the idea for active camouflage that can change its appearance to blend with different backgrounds.

“These are far-off ideas,” Mrksich said.