Joe Mindell spent a lot of time as a child wondering how things worked. He benefited from having an engineer for a father. Mindell says, “He understood and explained the inner workings of things beautifully to my brother and me. He had a very practical understanding of these things that profoundly opened up the world to us.” In addition to regularly taking books about math and science out of the library, Mindell looked forward to the elementary school science fair every year, so that he could delve into a project that would deepen his understanding of the world around him.
In high school, Mindell became interested in physics, especially in how it explained the world around him. He thought that he might major in physics upon entering Yale University, but he explains, “At the time, physics itself seemed focused on elementary particles, which were far enough from the everyday world that they didn’t draw me in.” He began taking classes in neuroscience, where he was first exposed to the idea of solving biological problems with concepts from physics. Around the same time, Mindell read The Double Helix by James D. Watson, and “was struck by Watson talking about how understanding helical diffraction required thinking about Bessel functions. And even though I didn’t know what those were, it clearly confirmed the connection between mathematical thinking and biological problem solving” Mindell says. These formative experiences convinced Mindell to study molecular biophysics and biochemistry, in which he received his Bachelor of Science degree.
After graduating from Yale, he studied at Albert Einstein College of Medicine and earned a combined MD-PhD. He completed his PhD work in Alan Finkelstein’s lab, using electrostatic analysis of charges on diphtheria toxin channels as a tool to map their membrane topology. He then completed a residency at Brigham and Women’s Hospital with an eye toward becoming a nephrologist, due to his interest in renal salt transport. Mindell found, however, that he was more drawn to a life in research than to pursuing a career as a medical doctor, so he joined Christopher Miller’s lab at Brandeis University as a postdoc. In Miller’s lab, Mindell worked on the ClC family of chloride channels. “For the first few years I was cloning new homologs of the family from the shark, which has an interesting salt transport system. Unfortunately, in the end, the proteins I found were frustrating, as they did not lend themselves to further work,” he says.
He then began to work on membrane protein structural biology. Mindell says, “I was able to form two-dimensional crystals of a ClC which led to the first structural pictures of this family of proteins.” Soon after Mindell left Miller’s lab, however, Miller discovered that the protein Mindell had worked on was not a channel at all, but rather a proton-coupled chloride transporter. Given his previous interest in transporters, from his days working with kidneys, Mindell decided to embrace this revelation. He explains, “I went with it and gradually shifted my whole lab to study transporters, which are generally much less well understood than ion channels.”
Mindell continues to work with transporters today, as a Senior Investigator in the intramural program at the National Institute of Neurological Disorders and Stroke, NIH. His lab studies structure-function relationships in secondary active transporters, focusing on bacterial homologs of important mammalian transporters, which Mindell explains, “are amenable to many kinds of experiments not available for their mammalian counterparts.”
The second major project of his lab concerns acidification of intracellular organelles. “This process is driven by a v-type ATPase,” says Mindell, “but, since the ATPase is highly electrogenic, other ions must be moved across the membrane to dissipate the built-up charge.” Currently, they are using combinations of modeling, cell biology, imaging, and transport measurements to try to get an accurate picture of the ion movements contributing to acidification, and to determine the combinations of transporters used in this process.
In addition to the science itself, Mindell finds the collegiality of research to be one of the most rewarding aspects of his work. He says, “We all know that the stereotypical view of the lone scientist off on his own is wrong. Our contact with the people around us has tremendous influence on our work…the social exchange of ideas is one of the things that I look forward to everyday when I go to work.” Mindell’s friends in the biophysics community find him to be particularly skilled at this sort of collaborative work. Kenton Swartz, one of Mindell’s close colleagues at NIH, explains that the two have had a major influence on each other’s projects, despite collaborating formally only on rare occasions. Swartz says, “We have had joint lab meetings and journal clubs for about twelve years now, and have mentored each other’s students and postdoctoral fellows. Joe’s fingerprints are on every piece of work that has come out of my laboratory in the last decade—we have perfected the role of highly interactive colleagues.”
Merritt Maduke met Mindell when both were postdocs in the Miller lab, working on discovering and characterizing the first prokaryotic ClC family member. She recalls that, “Joe was able to really push the project forward by determining the two-dimensional structure of ClC-ec1 by cryo-EM. He did beautiful work and was exceedingly gracious and generous in sharing the credit.” They are not currently working together, but Maduke frequently calls him to get his advice on difficult problems, and to enjoy his friendship. “He is really smart and always willing to talk,” she says, “He is also very witty in insulting his friends – in a loving manner. It took me awhile, but I knew I had finally gained his respect when he got around to insulting me.” Throughout his career, Mindell has let his sense of humor shine. Miller says, “He had the chops —a quantitative chemist/biophysicist at heart —and he had the wicked, wicked sense of humor that endeared him immediately to everyone in our group.” Another colleague Mindell met at Brandeis, H. Ronald Kaback, recalls a time when Miller and Mindell teamed up to play a prank on him during a presentation. He says, “Joe and a few other comedians under Miller’s influence sat in the audience and simultaneously shined laser pointers on the screen during my presentation. The effect was uproarious, as I could not tell which spot was mine.”
Mindell’s balance of serious science with a fun and collegial environment was modeled by his PhD and postdoc advisors, Finkelstein and Miller. Mindell says, “They share an incredible passion for science and an incredible level of scientific rigor. They are also both a bit looney and very funny. I learned from them that you don’t have to stop having fun to be an extremely serious scientist.” Mindell extolls the virtues of developing this sort of balanced attitude for those just starting out in their scientific careers. “I love what I do, and I can’t really imagine doing anything else,” he says. “For young people who feel this way too, I suggest they find a problem they really love and attack it with vigor. If they are creative, hard-working, and passionate, they can succeed and there’s no better life!”