Murphy receives prestigious NSF CAREER award
ssistant Professor William Murphy derives inspiration for his work as a tissue engineer from studying the complex processes through which human cells develop into tissue, limbs, organs and the like. “As these organs and limbs develop, cells on one end of the tissue have to differentiate into a different cell type than cells on the other end of the tissue,” he says.
That’s where protein concentration gradients do their work. For his National Science Foundation CAREER Award research, Murphy hopes to generate materials that deliver such gradients to stem cells—in this case, adult human stem cells isolated from bone marrow—in a controlled way.
During natural tissue development, stem cells often exist within high and low protein concentrations, with a gradual decrease in concentration—the gradient—between. “As the tissue grows, you’ll see these spatial gradients form and ultimately go away,” says Murphy. “So, they’ll form for some period of time, go away, and a new gradient will form. Ultimately, this provides one of the mechanisms that allows for organization of tissues and organs.”
The entire process sounds relatively straightforward—but in reality, replicating it to engineer tissue is extremely complex. It’s possible, says Murphy, to generate protein gradients, and it’s possible to ask, for example, some simple questions about how one protein affects one cell type. “Part of the issue is that, in vivo, cells are exposed to so many proteins and the gradients are so widely variable in their properties, concentrations, and slope of the gradient, that it’s very difficult to identify initial conditions that we’d want to explore,” he says.
To eliminate much of that guesswork, Murphy has developed an array-based approach that enables him to study, simultaneously, the effects of hundreds or thousands of different gradients on stem cells in three-dimensional culture. As a result, he is more likely to identify a gradient that will significantly affect cell behavior. “We have a better chance of collecting data that are relevant to in vivo development, and also data that are relevant for tissue engineering applications,” Murphy says.
He hopes to mimic protein concentration gradients in his efforts to engineer tissue. Now, he is attempting to create biomaterials in which the stem cells initially are homogeneous, but are exposed to heterogeneous signaling environments. “If we can spatially control whether they’re alive, first, in different parts of the material, and then second, whether they then differentiate into a particular mature cell type, then we have a pretty powerful approach for trying to engineer tissues.”
Murphy, who also maintains affiliations with the Departments of Materials Science and Engineering, Pharmacology, and Orthopedics and Rehabilitation, conducts research at the interface between biology, chemistry, materials science, and engineering.
His educational plan also is interdisciplinary: With funding from the Graduate School and the Stem Cell and Regenerative Medicine Center, he has introduced a graduate-level fellowship program in stem cell bioengineering, biology and public policy. “The purpose of this is to allow students who have a specialty in one of these three areas to spend dedicated time in one of the other two areas,” he says. “They have an immersion experience in that field. It broadens their perspective and hopefully creates some of the leaders of interdisciplinary research for the next generation in science and engineering.”
Hoping to create a culture and mindset of interdisciplinary research in young students, and in particular, traditionally underrepresented students, Murphy is establishing a mentorship program in which he and his graduate students will expose the undergraduates to interdisciplinary research as their first research experience. He also has modified his graduate-level course in stem cell bioengineering and now offers the course to undergraduates.
Already a prolific and engaging hands-on science presenter, Murphy plans to draw on established outreach mechanisms, including the university’s Science Expeditions event
and the WiCell summer science camps, to engage kindergarten through 12th-grade students in interdisciplinary research and in stem cell bioengineering.
