Richmond, VA (October 24, 2016)- Daniel E. Conway, Ph.D., assistant professor in the Department of Biomedical Engineering, has received a five-year, $1,800,000 grant from the National Institutes of Health for a research project to study the role of mechanical forces across proteins in epithelial cells. Epithelial cells separate the body from the outside environment and are the cells that provide a physical barrier in skin, lungs, and the intestines. Conway will study how mechanical forces at both cell-cell junctions and the nucleus contribute to growth, wound repair, and barrier function in these cells.

“Although it has been long-known that cells experience and respond to mechanical forces, it has been difficult to study how cells physically sense these forces at a molecular level. Recent advances in measurement techniques have allowed our group to develop new tools to measure forces within the cell with protein-specific resolution. We have focused specifically at cell-cell junctions because this is how cells are physically connected together and likely where a cell would sense pulling and pushing forces from neighboring cells. Our preliminary data indicate that these forces guide cell growth and cell movement," Conway said.

“We also have chosen to focus on measuring mechanical forces applied onto the nucleus. A current hypothesis in the field is that mechanical forces applied to the outside of the cell reach the nucleus, where the forces may regulate gene expression. Using a new force biosensor, my group has shown is that there are actually mechanical forces on the outside of the nucleus and that these forces are dynamic,” he said. “Now that we know these forces are present we are trying to understand if forces on the nucleus mediate a change in gene expression.”

To help answer this question, Conway is developing force biosensors to measure mechanical loading of proteins in cell-cell junctions and the nuclear membrane. To do this he inserts a molecular-level strain gauge in individual proteins. This force probe consists of a molecular spring between two fluorescent proteins. Using a technique known as FRET, he can measure changes in force observing changes in the spring’s length.

Conway describes himself as “an engineer who loves cell biology” and thinks the junction of the two disciplines creates a productive synergy.

“What drives cell biology forward are new techniques for measuring and imaging,” he said. “And often that is the role of the engineer, to design those new approaches.”

The grant is from NIH’s National Institute of General Medical Sciences (NIGMS), which funds science and innovation with applications to a variety of medical endeavors. While Conway’s investigations are likely to produce insights into tissue development, as well as diseases such as cancer, fibrosis and chronic inflammation, his award is not disease-specific. His award was funded as a Maximizing Investigators' Research Award, a new pilot mechanism by NIGMS to provide researchers with greater flexibility.

“We have ideas of what we want to do based on data we have collected, but sometimes the hypothesis is wrong. Sometimes even though it was right, you discover something that takes you in such a new, interesting direction that you go that way,” he said. “Science kind of wanders. It’s really dynamic.”