March 1, 2007 -- Martin Schwartz, professor of microbiology and biomedical engineering, and Douglas DeSimone, professor of cell biology, have been awarded a $500,000 grant by the Office of the Vice President for Research and Graduate Studies at the University of Virginia for their pioneering research in cell morphogenesis.
The award was made possible by funding designated by the Commonwealth of Virginia to build research capacity in the areas of bioengineering and regenerative medicine in 2006-08. “This grant is designed to encourage innovative and multidisciplinary research that may be considered high risk by traditional grantmakers, but that has the potential for high impact in the areas of morphogenesis and regenerative medicine,” says R. Ariel Gomez, vice president for research and graduate studies. “The research proposed by Schwartz and DeSimone is on the cutting edge and was chosen for funding through a competitive, external, peer review process.”
Schwartz and DeSimone are partnering to examine the role of physical forces in influencing gene expression during the earliest stages of embryo development and in the ongoing shaping of cells and tissues. “This is a real frontier area — there has been interest in cell behavior for a long time and a recognition that mechanical forces have an impact,” says Schwartz. “But this area is not well understood.”
Physical force is critical, for instance, to the health and vitality of cells. Disturbances in blood flow through the arteries leads to plaque build-up or atherosclerosis—which can eventually cause blood clots, heart attack and stroke. Likewise, force, or weight-bearing exercise, is recommended to increase bone mass in individuals at risk of osteoporosis. Still, fundamental questions about morphogenesis — or the shaping, growth, and differentiation of cells, tissues, organisms, and organs — remain unanswered. Schwartz and DeSimone hope to find answers to some of these questions through their cooperative research.
“This research represents truly creative and collaborative approaches by Schwartz and Desimone and combines the disciplines of cell biology with biomedical engineering,” says Arthur Garson Jr., dean of U.Va.’s School of Medicine. “Their work will help us understand how mechanical forces within and outside cells and tissues are organized into biochemical information that will turn genes on and off, and ultimately regulate development. Until now, this area has been poorly understood, largely because of technical hurdles.”
Schwartz’s lab is devising novel methods to measure molecular forces in vivo. Schwartz is “pushing the envelope on imaging technology,” comments DeSimone. Schwartz’s tool will enable the real-time viewing of the forces within living cells—something that has not been possible before.
With the help of the DeSimone lab, the sensor technology will be applied to embryos of Xenopus laevis, a species of African frog, in order to directly observe the forces that drive gastrulation — the transition from ball of cells to multilayered embryo that occurs in animals. “During this early development, cells undergo the most fantastic movement — there are serious forces at work,” notes Schwartz. DeSimone is particularly interested in understanding how mechanical forces are translated into biochemical signals that influence patterns of genes expressed by embryos. He plans to place individual frog cells and tissues on substrates that can be stretched and pulled in a variety of ways and then identify those genes that are turned on or off by these mechanical signals. Schwartz and DeSimone expect to find cues through this research about what enables the cells to move, grow, and signal in response to these forces.
Xenopus laevis embryos are conducive to this project because much is known about the details of their cellular movements. DeSimone points out that much of this knowledge was derived from the work of colleague Ray Keller in the U.Va. Department of Biology. In addition, unlike the embryos of mammals, frog embryos are completely self-sufficient, containing all of the nutrients they need to develop outside of the mother. Thousands of eggs are laid at a time, providing ample opportunity to gain insights into how organisms begin to organize themselves. This frog research “is very much applicable to higher order development,” notes DeSimone.
Brian Helmke, assistant professor in biomedical engineering, and Ammasi Periasamy, research professor in biology, will collaborate with Schwartz and DeSimone on the project. The two-year award will allow the team to hire postdoctoral research associates and graduate students, as well as pay for microscope time.
The practical implications of this research are substantial. “It may allow us to approach intelligently how to engineer tissues in the laboratory,” says DeSimone. In addition, because cancer cells react and respond to the forces and signals around them differently than normal cells, a better understanding of these intricate cellular processes could be key to halting the progression of cancer.
Written by Melissa Maki, research communications coordinator for the Office of the Vice President for Research and Graduate Studies.