Jim Weisshaar, Professor of Chemistry at the University of Wisconsin, Madison, came late to biophysics, after studying gas phase collisions and spectroscopy using lasers and molecular beams as a physical chemist for 25 years. “In 1997,” he says, “I spent a sabbatical year with Ed Samulski at UNC Chapel Hill studying the structure of alanine dipeptide in liquid crystalline media. Assigning those many sharp lines arising from dipolar couplings got me interested. A few years later, I dropped the gas phase and started learning single-molecule fluorescence. I call it my ‘scientific mid-life crisis,’ to distinguish it from the other ones.”
Weisshaar first became engaged in science during his high school chemistry class. He was lucky to have a teacher, Richard Burke, who believed in the abilities of his students. Weisshaar recalls, “He had us solving the Schrodinger equation for the hydrogen atom in Chem II! I thought quantized atomic energy levels that could be computed accurately were amazing.” Recently, the two reconnected. “Mr. Burke called me up out of the blue. I hadn’t spoken with him since high school days. Evidently he had googled me. It was a special treat catching up with him, now 72 years old and running his own farm.”
After high school, Weisshaar attended Michigan State University, where he earned his bachelor of science in chemistry. He then went on to the University of California, Berkeley, where he completed his PhD in chemistry with Brad Moore as his advisor. Weisshaar completed his postdoc at the University of Colorado, Boulder, working on gas phase ion collisions under Steve Leone, Barney Ellison, and Veronica Bierbaum. Following his postdoc, Weisshaar landed at the University of Wisconsin, Madison, where he established himself in the Department of Chemistry. He worked happily in physical chemistry for twenty-five years before changing fields. “Changing fields from gas phase physical chemistry to biophysics has been a huge challenge,” Weisshaar says. “It turns out that all the molecular quantum mechanics I knew became instantly irrelevant. Now I need stat mech and thermo! On the other hand, my quantitative instincts from [my] physical chemistry days have served me well. Learning enough cell biology to be able to talk with those folks in their own language has been the hardest part. That’s a continuing challenge. The Department [of Chemistry at the University of Wisconsin, Madison] was very patient during the transition years.”
William Moerner of Stanford University and 2014 co-recipient of the Nobel Prize in Chemistry is a colleague in the single-molecule field who has watched Weisshaar’s transition into biophysics over the past decade. Moerner says, “In the mid-2000s, he switched from more conventional physical chemistry to biophysics, and he has become a leader in the use of single-molecule studies to understand a variety of biophysical problems such as diffusion in membranes and super-resolution analysis of bacterial protein distributions…He is a friendly, deep colleague who always presents a careful, incisive analysis.”
Weisshaar’s longtime colleague at Wisconsin, Tom Record, admires the transition Weisshaar has been able to achieve. “He made a remarkable transition from gas phase chemical physicist to molecular and cellular biophysics,” Record says, “[He has been] successful as a researcher and grad student mentor in both endeavors.”
Biophysics draws on genetics, cell biology, molecular biology, biochemistry, physical chemistry, optics, and condensed-matter and statistical physics. We all need to continually broaden our intellectual, experimental, and computational horizons in order to be able to see research opportunities and take advantage of them. That’s not easy, but this ‘intrinsic interdisciplinarity’ is part of what makes biophysics so fascinating.
-Weisshaar
For his part, Weisshaar is happy to be part of the biophysics community. “Our field spans a tremendous range of intellectual activity,” he says, “Biophysics draws on genetics, cell biology, molecular biology, biochemistry, physical chemistry, optics, and condensed-matter and statistical physics. We all need to continually broaden our intellectual, experimental, and computational horizons in order to be able to see research opportunities and take advantage of them. That’s not easy, but this ‘intrinsic interdisciplinarity’ is part of what makes biophysics so fascinating.”
The Biophysical Society has become a scientific home for Weisshaar. “The meetings are a good way to learn a lot in a short period of time. The poster sessions are great – that’s where you learn from the students what’s really going on! [The meetings have] helped me meet people I’ve wanted to meet based on their publications. Those stimulating meetings naturally generate research ideas.”
Currently, Weisshaar uses single-molecule fluorescence to study how ribosomes and RNA polymerase work together in space and time in live E. coli cells. His lab also studies how antimicrobial peptides (AMPs) attack live bacterial cells in real time in order to understand how they kill cells, something he became involved in unexpectedly. He says, “We were studying GFP diffusion in the E. coli cytoplasm and I gave a talk at the University of Pennsylvania…Dr. Robert Bucki came up to me afterwards and suggested we watch antimicrobial peptides in action. I am eternally grateful! The single-molecule tracking projects popped up when the new localization methods appeared.”
Weisshaar’s lab recently discovered that certain AMPs induce formation of reactive oxygen species in the E. coli cytoplasm. Weisshaar explains, “That’s a new ‘symptom’ after AMP attack, and it’s an important part of bacteriostatic action in aerobic growth conditions. We’re trying to understand how that happens and how ubiquitous the phenomenon is.” They also suspect that AMPs may be inducing opening of mechanosensitive channels in the E. coli cytoplasmic membrane, allowing proteins and small solutes to traverse the membrane. He says, “That’s a very different picture than the usually invoked mechanism of pore formation by insertion into the membrane. A lot more work needs to be done.”
Anne Kenworthy, a friend and biophysicist at Vanderbilt University, says, “Jim is a very thoughtful and creative scientist. His recent studies have made good use of super resolution microscopy and other high-end imaging approaches to study bacteria. This has allowed them to visualize some remarkable events, such as bacteria under attack by anti-microbial peptides.”
Weisshaar has found that the most rewarding aspects of his work has been those rare moments of discovery. He elaborates, “I guess we all love those ‘aha’ moments when we figure out something that has been puzzling you for a long time, or we finally do the incisive experiment. This happens several times a year if I’m lucky.” Outside of the lab, he finds fulfillment in a variety of hobbies, including gardening, reading, and photography. He also enjoys riding his bicycle, he says, “but only seven months of the year in Madison.”
For young scientists, Weisshaar offers this advice: “Work hard on your communication skills, both written and verbal. In an era of highly competitive funding, that’s becoming more important all the time.”