PROVIDENCE, R.I. [Brown University] — Few people could possibly know better than Chris de Graffenried how much the context provided by place can matter. A true global citizen by the time he was in sixth grade, de Graffenried has settled at Brown, where he studies the crucial difference that precise location of organelles within cells makes in the biochemistry of cell structure. That research could have a direct impact on the fight against diseases, such as sleeping sickness, caused by single-celled parasites.
With a Colombian mother and an American father in the emerging markets banking business, de Graffenried was born in Venezuela and spent time in Africa and the Middle East before arriving in Connecticut at the age of 11.
As an undergraduate at Carleton College in Minnesota he studied chemistry without an inkling that he’d ultimately join the company of biologists. But one day in graduate school at the University of California–Berkeley, he attended a conference where an eminent cell biologist stated that the localization of enzymes within a cell has everything to do with what they do.
“He said it doesn’t really matter what’s going on when you look at things in the test tube because what’s going on in the cell is so much more complex and organized,” said de Graffenried, assistant professor of molecular microbiology and immunology. “Proteins encounter each other in very specific environments within cells that are usually delimited by membrane compartments with unique biochemical signatures that do specific things.
“As a chemist I was confronted by the fact that all this in vitro enzymology and biochemistry we were doing was really limited by a lack of understanding of where in cells things are and how the cell orchestrates biochemical reactions.”
So his thesis, under the supervision of Carolyn Bertozzi, focused on how localization in an organelle called the Golgi apparatus affects the behavior of a class of enzymes involved in the production of sulfated carbohydrates.
As a postdoctoral researcher, de Graffenried decided to study the cell biology of sleeping sickness. While thankfully on the decline, it remains an awful disease in which a tsetse fly bite introduces the parasite which eventually causes massive inflammation in the brain. What de Graffenried has learned is that the parasite’s streamlined shape, which helps it swim, must be passed to the daughter cells when the parasite divides. The duplication process requires a precisely orchestrated series of events so that all the essential cellular compartments are not only duplicated but positioned correctly. Disrupting this function could disrupt the parasite’s swimming.
“That shape is essential for its function,” he said. “If they can’t swim, they can’t survive.” During his postdoctoral work, de Graffenried identified a key enzyme that appears to function as a master orchestrator of trypanosome cell division, which is currently the main focus of his lab.
Humans also have the same enzyme, but in us it behaves very differently, so there is an open door for a treatment that targets the enzyme precisely enough. The hope is that disrupting the enzyme could treat the disease. The approach may be a viable model for treating other small parasites as well, he said.
De Graffenried has continued to advance this line of research since coming to Brown in 2014 with his wife, Amanda Jamieson, also an assistant professor in his department. Before coming to Brown, they were at the Max F. Perutz Laboratories in Vienna, Austria, for five years.
Brown is a great place for them, he said. The department is rare in combining microbiology and immunology, which suits them well. After a long time overseas, Providence also seems like a great place to raise their child.
And at Brown, de Graffenried has also been enjoying the chance to work with students. Two talented undergraduates, junior Zemplen Pataki and sophomore Celina Hsieh, work with him in the lab, for example.
“I really get a lot of satisfaction out of watching them start from not really knowing how to do much to really being able to fully run experiments on their own,” he said. “They are really capable.”
And he now teaches the university’s “Phage Hunters” class, in which first-year students get an introduction to biology by finding, characterizing, sequencing, and naming novel species of microbes they can find in the campus soil.
“For me the thing that’s most important about the class is to get people excited about science,” he said.
It’s no surprise that he wants to make the class an inspiring place to learn.