It was a dry November day in 2005 and Peter Lloyd Jones had wandered out from his usual turf in the Vagelos Laboratories, where he makes his home within the Institute for Medicine and Engineering (IME). Jones is an associate professor of pathology and laboratory medicine, and currently directs the Center for Pulmonary Arterial Hypertension Research. If his professional titles suggest a double dose of introversion, he resolutely plays against stereotype. In his office there is an Oscar Wilde action figure propped up against a wall-mounted marker board. The Irish playwright’s penchant for wit often finds a reflection in the British pathologist’s banter. “My favorite quote,” Jones told me, “is: ‘A true friend stabs you in the front.’”
Jones can’t remember exactly where he was going that day in November, but his unexpected detour remains vivid. “I think I was walking to get some coffee, and there was a sign: Non-Linear Systems Organization,” he recalls. “And I thought, I’m a non-linear systems biologist. I’m going to walk in.”
The NSO is a research group that had recently been started within the School of Design under the leadership of Cecil Balmond, an internationally renowned structural engineer and the Paul Philippe Cret Practice Professor of Architecture. Its first annual conference was taking place in Meyerson Hall. Most of the participants hailed from university architecture departments around the country, plus the odd mathematician, engineer, and software designer. They had gathered to address questions like: “How can scientific models of complex phenomena in mathematics, nature, and the universe be most effectively employed in the design and fabrication of structures for human life and enjoyment?”
Jones wandered in and was “completely blown away” by what he heard. There weren’t any biologists among the speakers and panel moderators, but some of the ideas they were batting around evoked striking parallels to his own work.
Like an increasing number of his colleagues in the life sciences, Jones has entered what is sometimes called the postgenomic era of biological research. Before the sequencing of the human genome was completed in 2000, the reigning assumption among molecular biologists was that each protein manufactured by our bodies derived from a unique corresponding gene, and that the destiny of a given cell was driven by the genetic code it carried. But the data that came out of the Human Genome Project told a different and much more complicated story. Our bodies make some 90,000 distinct proteins—the chief actors within cells—from a mere 30,000 genes. Furthermore, evidence is accumulating that a cell’s local environment can exert a dominant influence over gene expression—which can in turn impact that very same microenvironment. Understanding these non-linear, dynamic feedback loops has become one of the major challenges of contemporary biomedical research.
What this means in terms of human health and disease is explained by Anne Plant, a biochemist at the National Institute of Standards and Technology in Washington. “It’s becoming more and more appreciated,” she says, “that if you put cells in one kind of extracellular-matrix environment, or another extracellular-matrix environment, and treat them otherwise exactly the same—with the same chemical stimulants or the same pharmaceutical agents—you will get different responses.”
The average high-school biology teacher probably doesn’t spend much time on the extracellular matrix, but animal life would be all but impossible without it. The ECM is the connective tissue that provides structural support to living cells, giving them a sort of scaffolding to which they can anchor. It also regulates communication between cells, stores and releases chemicals that can trigger a range of cellular functions, and governs the movement and migration of cells through its intricate architecture. The complexity of the system beggars description. The components of extracellular matrices are manufactured inside of their resident cells, which then fall subject to the influence of structural and biochemical changes within the scaffolds they have excreted.
The far-reaching influence of the ECM has profound implications. “You could potentially treat diseases and cause cell behavior to change by changing the extracellular matrix’s elasticity,” for example, says outgoing IME director Peter Davies, the Robinette Foundation Professor of Cardiovascular Medicine and a professor of bioengineering as well as pathology and laboratory medicine. “And in fact, in breast cancer it works,” he says. “If you change the matrix’s physical properties, you can cause an epithelial tumor in culture to reorganize back to its normal form—rather than being a cancerous cell which grows all over the place. And its metastatic potential declines precipitously.
“You could imagine,” Davies continues, “that instead of—or in addition to—treating a breast tumor with chemotherapy or radiotherapy, you could also alter the environment around the cell by micro-injecting a gel of some kind, or a matrix with properties that you know favor the maintenance of normal.”
In other words, differences or changes in tissue architecture can have major repercussions on the development and treatment of disease. This “radical but true notion” was already apparent to Jones when he walked into the NSO conference. But he walked out with a novel idea: maybe architects would be able to look at the tissue systems in his lab and see things that he was overlooking, or didn’t know how to analyze. The person who would help him shape and realize this vision was NSO founding member Jenny Sabin, a lecturer in the School of Design.
An Architect Walks Into the Lab By Trey Popp
Physical models of the cell cluster.
Models by Sabin, Wang, and Jones; photo by Candace diCarlo