by Silvia Cavagnero and Marina Ramirez-Alvarado
Susan Lindquist was born in Chicago in 1949. Her father worked as a contractor and her mother was a homemaker. Sue showed an interest in the natural world as a child, and excelled in her science classes. She attended the University of Illinois at Urbana-Champaign as an undergraduate, where she received her bachelor’s degree in microbiology. She went on to graduate studies at Harvard University, earning her PhD in biology in 1976. She undertook a postdoctoral fellowship at University of Chicago, where she remained for 23 years as a professor. Sue then moved to the Whitehead Institute for Biomedical Research and MIT, later also joining the Broad Institute. She also served as a Howard Hughes Medical Institute Investigator from 1988-2001 and from 2006 until her death from cancer in October 2016.
Sue made many key discoveries in the field of protein folding in the cell, and is one of the few scientists who unveiled and understood how molecular chaperones, including Hsp104 and Hsp90, enable protein folding and preserve the health of eukaryotic cells and entire organisms, including humans. She highlighted the importance of the Hsp90 chaperone in human disease, especially cancer. Sue also made key advances in the field of prions. After years of controversies, it is now well known that prion proteins are characterized by a native folded state and by one (or more) additional aggregated states able to catalyze the conversion of the native state to aggregate. Sue focused on the study of prion proteins in yeast cells, capitalizing on the knowledge that they bear a huge genetic similarity with human cells. Yet, yeast is much easier to grow and genetically manipulate, rendering scientific discovery way more efficient. Among many other discoveries, Sue showed that the Hsp 104 molecular chaperone present in yeast is required for the prion-like behavior of the sup35 protein. Just a few months ago, she published a seminal study showing that evolutionarily conserved intrinsically disordered regions in yeast proteins (not previously known to be prions) have the ability to impart inheritable, and often beneficial, traits to yeast cells. This finding is one of Sue’s legacies, and may prove to be of general significance in the years to come.
Marina Ramirez-Alvarado, Mayo Clinic and chair of the Biophysical Society Committee for Inclusion and Diversity, recalls, “I first met Susan Lindquist at a conference while I was a postdoctoral fellow at Yale. At the time, I was very interested in the molecular determinants of amyloid formation and Sue had contributed (and continued to do so) to the understanding of amyloid propagation using yeast prions. Together with Andrew Miranker, then an assistant professor of molecular biophysics and biochemistry at Yale, I started a misfolding journal club. We reviewed all of the manuscripts from numerous leaders in the field, and Sue’s papers were some of the first articles we reviewed during our journal club.”
One beautiful example of Sue’s innate ability to communicate science in an effective and creative way is her 2012 lecture on protein folding at the National Institutes of Health’s Celebration of Science event. You can view this powerful presentation here: https://www.nih.gov/news-events/videos/celebration-science-
dr-susan-lindquist. Silvia Cavagnero, University of Wisconsin, Madison, says, “We have been routinely recommending this video to undergraduate and graduate students interested in learning more about protein folding, and we have always received rave comments back.”
Sue has always been admirably frank and spontaneous with anyone talking to her, and even more so during her scientific lectures and oral presentations. For instance, she used to share the difficulties she had in publishing some specific studies, during her talks at conferences and universities. She sometimes discussed the fact that manuscript and grant reviewers were not always in her favor. What was so special about her spontaneity was not only her courage in admitting the presence of barriers or obstacles in her science and career, it was the fact that she stood firm and strong defending her findings and their originality while keeping a cheerful attitude and good humor. Her joy in doing science and fearlessness in the face of adversity was a powerful message to other scientists, especially young scholars.
Sue was also a role model to women in science, especially those she trained. Many of her female students and postdocs have gone on to successful careers in academia and industry. The halo of optimism that Sue infused into people stayed with them for life.
In a 2016 profile with The Scientist, Sue recalled how being a young female scientist in academia gave her no expectation to get tenure. With that in mind, she had no fear when making risky choices in her career, as she did not expect she had much to lose. Of course her intuitions on the importance of changing model organism proved to be not only timely but also visionary, and she was rewarded with tenure and much more throughout her career.
Marina remembers seeing Sue speak in 2005 at the Proteins Gordon Conference in New Hampshire. “[Andrew Miranker and I] miscalculated the time it would take us to drive from
Connecticut to New Hampshire, and we were going to miss the first part of the keynote speaker’s lecture. Yes, you guess right, Sue Lindquist’s. So Andrew and I start guessing what Sue will be saying in the first 15 minutes of her presentation that we are going to miss,” she shares. “We arrived, sat in the back row and found out that they were starting late, and we had not missed a thing. During this lecture, she mentioned that her brilliant postdoc, who did the work they had just published in Nature and she was presenting, was stuck in India after he went there to marry, due to immigration issues post 9/11. Again, within the brilliance of her science, her humanity came through.”
“I interacted with her again as I acted as editor-in-chief for a protein misfolding book and asked her to write a chapter on yeast prions. She was prompt, responsive, and helpful during the 5-year process of designing the book, inviting people to contribute, reminding them of the multiple deadlines, and reviewing and proofing chapters,” Marina shares. “Sue’s legacy is the numerous people she trained… her inspiration to a generation of female — and male — scientists to believe in what we are doing and keep working hard. We will miss you Sue.”
Following her passing, colleagues recall her excitement for discovery, constant striving, and ability to communicate her science to broad audiences, in addition to the importance of her work, both as a researcher and a mentor.