Chad Rienstra’s scientific career was jumpstarted by four years of undergraduate research, where he developed a broad interest in biology, chemistry, physics, mathematics, and engineering. It’s this commitment to interdisciplinary research and education that he brings to bear years later as he joins the University of Wisconsin–Madison Department of Biochemistry as a professor.
After his undergraduate experience at Macalester College in St. Paul, Minn., he attended MIT for graduate school, followed by a postdoc at Columbia University. In 2000 he started at the University of Illinois, was tenured in 2008 and promoted to full professor in 2013, before joining UW–Madison this year.
Throughout this journey there has been one common thread — his interest in nuclear magnetic resonance (NMR), a scientific technique that allows scientists to measure the unique properties and structures of proteins, as well as other biomolecules and chemicals.
“I had an experience when I was an undergraduate, and then again in my postdoc, where my institution was getting a new magnet to use in NMR and I was tasked with helping with the installations,” Rienstra says. “It was so fascinating and formative for me to follow around the engineers to learn about the instruments and how they work. NMR had seemed like magic to me — you push a button and get a result — but the more I learned, the more interested I became in the guts of how NMR spectrometers work and how they can work better.”
In NMR experiments, samples of interest are placed in a probe and then placed inside a powerful magnet. The probe contains a special type of antenna, or "sample coil", to communicate with the nuclei inside the powerful magnetic field. Radiofrequency signals are sent to the sample through the probe in a series of magnetic pulses (so-called "pulse sequences"), which cause the nuclei of sample atoms to respond. "It's sort of like a game of 20 questions," Rienstra says, "the more precise questions you ask, the more you learn about the sample."
These answers are also picked up by the probe and stored in the receiver, where they carry vital information that allows scientists to learn about the molecules in the sample. In the specific experiments Rienstra performs — called solid-state NMR — the probe also spins the sample very rapidly at a “magic angle” to collect better data.
It is these probes that are at the heart of Rienstra’s research. His lab performs experiments and collects and analyzes data using solid-state NMR, as well as engineers new probes, pulse sequences, and computational programs that help them better collect, analyze, and make use of data.
“The probe is the part of the instrument that interfaces the sample with the magnet,” he explains. “Probes have critical effects on performance in every possible way and really determine the quality of NMR data you can get in an experiment.”
The structural data and other information that NMR supplies researchers is essential for understanding and finding treatments for many diseases. For example, Rienstra’s lab studies aggregates of a protein (named alpha-synuclein) believed to be a cause of Parkinson disease. Since solving the structure of a form of the protein, they have been working with a neurologist to study patients with different types of Parkinson’s and other related diseases to see how the protein structures differ among them. The resulting structures could hold the key to better diagnosing and treating the diseases.
In another area of research in the lab, they are focused on the development of anti-fungal drugs, in collaboration with researchers at Illinois. One drug they are investigating (called amphotericin B) binds to fungal cells and extracts compounds (sterols) they need to survive. The problem is, it does the same with healthy human cells. Through their work they want to make it more effective but also less toxic to cells they don’t want to kill.
A final part of his lab is devoted to developing better NMR technologies, including tools and techniques for obtaining data as well as computer algorithms and software to analyzing the data more effectively. He says the two areas feed off each other. Necessity is the mother of invention so when they need to gather specific data using a method not yet developed, they take on the task.
“I’m constantly fascinated by this discipline and how many ways it can be applied, from MRI in the human body all the way down to studying small drug molecules and even how to make better batteries,” Rienstra says. “It’s amazing that on a given instrument there might be a biochemist, an organic chemist, a materials scientist, and a physicist, all of whom can use NMR to accomplish very important yet very different research objectives.”
During his career, Rienstra has been awarded a Howard Hughes Medical Institute predoctoral and postdoctoral fellowship, a National Science Foundation Faculty Early Career Development Program (CAREER) Award, among others. He is a fellow of the American Association for the Advancement of Science and a Cottrell Scholar from the Research Corporation for Science Advancement.
At UW–Madison, Rienstra will co-direct, along with biochemistry professor Katherine Henzler-Wildman, UW–Madison’s world-renowned National Magnetic Resonance Facility at Madison (NMRFAM), which is housed in Biochemistry and serves as both a campus and national resource. He has already brought in three 600 MHz magnets that were installed over the last month, and a 750 MHz magnet will be moving from Illinois in coming months. He is also expanding the number and types of probes to allow for a larger variety of experiments in NMRFAM, including for chemistry, materials, physics and engineering applications.
“This is one of the top NMR facilities in the world,” he says. “It strikes a great balance between having state-of-the-art instrumentation and being highly accessible to researchers, a difficult feat. There are multiple faculty members doing NMR research and a world-class staff of experts. It’s the type of environment that supports great research, where you can learn and collaborate with great colleagues. I’ve envied it for a long time and it's my dream job to be leading NMRFAM well into the future.”
Learn more at Chad Rienstra's faculty page.