“My research focus has always been to do things that nobody else can do, see things that nobody else can see. I like to pick really challenging topics and push the limits,” says Schuyler van Engelenburg, an assistant professor in the University of Denver’s Department of Biological Sciences since fall 2014.
Van Engelenburg is advancing the knowledge of the complex interactions between viral pathogens and human host cells to better understand how individual virus particles use infected cells’ own components at the cellular and molecular levels to multiply and thus cause illness. To do so, he literally peers inside individual human cells as they produce virus particles (called “virions”) and observes the action via what he describes as “a series of snapshots.”
He and a few scientific colleagues are indeed seeing what no one else has seen before.
Van Engelenburg’s current focus is on the process by which virions of the human immunodeficiency virus (HIV) “hijack” specific proteins naturally found in human cells to produce and release additional virions. This involves new three-dimensional imaging techniques at resolutions high enough to observe the molecules involved. His expertise is in superresolution fluorescence microscopy, or using powerful microscopes that can image molecular complexes in conjunction with fluorescence. Collaborating with other experts and building on earlier work, he has engineered the means to tag both the viral particles and human host cells with fluorescent proteins, enabling unprecedented levels of visualization.
“My work is on two fronts. First, it’s to label the virus so we can see it,” he says. “We wouldn’t be able to see it without fluorescent tags. We also engineered human or monkey host cells to contain a host-cell gene fused to a fluorescent protein to track the location of that protein within the cell. We engineered viral proteins to label them and tagged the host proteins being hijacked by the virus to map out the distribution of the proteins and their function.”
The modified virus particles and host cells were also tested to ensure that introducing the fluorescent tags only minimally disrupted their natural functions while maximizing the fluorescence signal.
Van Engelenburg also teaches a graduate-level survey course in microscopy techniques for biological science and biophysics students enrolled in the molecular and cellular biophysics (MCB) PhD program, which encourages collaborative approaches among physics, biology, chemistry, mathematics and related fields in researching biological problems, with a particular emphasis on biomedical issues.
“Interdisciplinary PhD programs centered on biophysics are uncommon, and I saw a lot of commitment here to expand,” he says. “It’s exciting to be part of a program growing in that direction.”
Van Engelenburg was born and raised in Colorado. He received his BS in chemistry from Fort Lewis College in Durango, Colo., and his PhD in biochemistry from the University of Colorado in Boulder. For his PhD work, he developed live-cell imaging techniques to study salmonella infection through inserting fluorescence into the bacterial proteins.
After completing his PhD and before coming to DU, van Engelenburg served for four years as an NIH postdoctoral fellow in the cell biology and metabolism program at the National Institute of Child Health and Human Development in Bethesda, Md. For his postdoctoral work, he shifted research emphasis from salmonella bacteria to the organization of protein structures involved in the production of HIV in host cells.
Van Engelenburg wants to advance the techniques for doing 3D superresolution microscopy with HIV in live cells. “If we can achieve success by viewing HIV budding at the superresolution scale in live cells, then we can gain new insights into how HIV hijacks the cell’s own machinery,” he says.
Another of his aims is to pass on his advanced knowledge of superresolution imaging to his students for the sake of future research. He has two talented undergraduates currently working in his research lab, assisting with multiple projects.
“It’s been a lot of fun seeing them progress and get excited with results as I teach them new laboratory techniques, from cell biology to molecular biology and microbiology,” he says.