Susan Lee Lindquist (1949–2016)

Susan Lindquist was internationally renowned for her pioneering discoveries that transformed our understanding of protein homeostasis and the wide array of biological processes it governs. She developed cutting-edge genetics and cell biology technologies; applied them on diverse organisms, including yeast, fruit flies, plants, cavefish, and humans; and tackled and solved previously intractable problems ranging from delineating cellular stress responses, to uncovering genetic variation in evolution, to the role of protein misfolding in human disease. Sue was born in Chicago in 1949 and grew up in a middle class suburb. She captured her spirited passion and cooking skills from her Italian-American mother, Eleanor, and developed her optimism and good nature from her Swedish-American father, Iver. Sue was flanked in age by two brothers, John and Alan, who are both softspoken and kind. They always seemed content to let Sue orchestrate family events, and as a natural leader and enthusiast of holidays, Sue relished these tasks. Sue was the only scientist in the family. She would continue throughout her life to break the mold in countless ways. Suewasanundergraduateat the University of Illinois, where she majored in biology. As a graduate student with Matt Messelson at Harvard University in the 1970s, Sue became interested in the Drosophila heat-shock response, with intent to illuminate the then murky world of gene regulation in eukaryotic cells. She isolated the mRNAs that code for heatshock proteins (HSPs) and showed that they derive from the chromosomal structures (puffs) that are remodeled upon an elevation in temperature. With PhD in hand, Sue moved to the University of Chicago, and after a brief postdoctoral study with Hewson Swift, she joined the faculty in the Biology Department there in 1978. In 1980, I came to the University of Chicago from MIT and became the only woman in the Biochemistry Department. Encouraged by our mutual friends in Boston, Sue and I sought each other out on campus. We instantly became friends, and our friendship continued to grow over the ensuing 36 years. In the 1980s, few women scientists were taken seriously. Through our friendship and mutual respect for each other’s science, we provided strong support for each other and were able to focus our careers on what mattered—improving our science, thinking outside the box, asking big questions, and being confident and fearless. Our research discussions and excitement about each other’s scientific findings gave us the fuel we needed to propel our science to a different plane. When four departments merged into two in the mid-1980s, Sue and I both joined the Department of Molecular Genetics and Cell Biology, as did all of the other women. Overnight, there was strength not only in numbers but in scientific talent. In 1988, Sue and I received HHMI appointments, and our labs were soon adjacent to one another. By this time, we were also teaching together, as we shared a passion for teaching, mentoring, and introducing students to the joy of cutting-edge science. These events facilitated our scientific interactions and solidified our friendship. It was a friendship built upon mutual admiration for each other’s science and intellectual prowess, as well as a shared love for music, dancing, eating good food, going to the beach, and enjoying life. Sue started her independent career by unveiling broader functions of the heat-shock response by employing yeast, plants, and mammalian cells. It was Sue’s idea to use yeast cells as ‘‘living test tubes’’ to empower studies of the very difficult biochemistry of inherently unstable proteins in crowded cellular environments. She began to turn the tables on prevailing views about HSPs. Hsp90 was thought to repress the activity of its interacting proteins. Sue showed that, by contrast, Hsp90 is actually key to their maturation and keeps them poised for activation by the correct signals. She established this regulatory mechanism for both Src tyrosine kinase and the glucocorticoid receptor. These otherwise unrelated proteins share metastable structures that facilitate the functional transitions associated with signal transduction. Sue’s work on vSrc was particularly insightful. She Sue dressed up for Halloween with Nora and Alana in 1994. Photo courtesy of the author’s husband, David Hansen.