Susan Lindquist


Susan Lee Lindquist, ForMemRS was an American professor of biology at MIT specializing in molecular biology, particularly the protein folding problem within a family of molecules known as heat-shock proteins, and prions. Lindquist was a member and former director of the Whitehead Institute and was awarded the National Medal of Science in 2010.

Early life and education

Lindquist was born in Chicago, Illinois, to Iver and Eleanor, and attended Maine South High School in Park Ridge.
Lindquist's father and mother were of Swedish and Italian descent, respectively, and although they expected her to become a housewife, Susan studied microbiology at the University of Illinois as an undergraduate and received her PhD in biology from Harvard University in 1976. She completed a post-doctoral fellowship at the American Cancer Society.

Career

Upon completing her dissertation in 1976, Lindquist moved to the University of Chicago for a short post-doc before being hired as a faculty member in the Biology Department in 1978, becoming the Albert D. Lasker Professor of Medical Sciences with the founding of the Department of Molecular Genetics and Cell Biology in 1980. At the University of Chicago Lindquist investigated the role of heat shock proteins in regulating the cellular response to environmental stresses. Lindquist pioneered the use of yeast as a model system to study how heat shock proteins regulate gene expression and protein folding. For this work, Lindquist was made an investigator for the Howard Hughes Medical Institute in 1988. After making important new discoveries to prions, Lindquist moved to MIT in 2001 and was appointed as Director of the Whitehead Institute for Biomedical Research, one of the first women in the nation to lead a major independent research organization.
In 2004, Lindquist resumed research as an Institute Member, an associate member of the Broad Institute of MIT and Harvard, and an associate member of the David H. Koch Institute for Integrative Cancer Research at MIT.
Lindquist was awarded the National Medal of Science in 2009, for research contributions to protein folding.
Lindquist lectured nationally and internationally on a variety of scientific topics. In June 2006, she was the inaugural guest on the "Futures in Biotech" podcast on Leo Laporte's TWiT network. In 2007, she participated in the World Economic Forum in Davos, Switzerland with other MIT leaders.
Lindquist also co-founded two companies to translate research into potential therapies, FoldRx in and Yumanity Therapeutics in, companies developing drug therapies for diseases of protein misfolding and amyloidosis.
In November 2016, Johnson & Johnson gave a $5 million gift to Whitehead Institute to establish the Susan Lindquist Chair for Women in Science in Lindquist's memory. The gift will be awarded to a female scientist at Whitehead Institute.

Research

Lindquist is best known for her research that provided strong evidence for a new paradigm in genetics based upon the inheritance of proteins with new, self-perpetuating shapes rather than new DNA sequences. This research provided a biochemical framework for understanding devastating neurological illnesses such as Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt–Jakob diseases. She was considered an expert in protein folding, which, as explained by Lindquist in the following excerpt, is an ancient, fundamental problem in biology:
What do "mad cows", people with neurodegenerative diseases, and an unusual type of inheritance in yeast have in common? They are all experiencing the consequences of misfolded proteins.... In humans the consequences can be deadly, leading to such devastating illnesses as Alzheimer's Disease. In one case, the misfolded protein is not only deadly to the unfortunate individual in which it has appeared, but it can apparently be passed from one individual to another under special circumstances – producing infectious neurodegenerative diseases such as mad-cow disease in cattle and Creutzfeldt–Jacob Disease in humans.

Lindquist worked on the PSI+ element in yeast and how it can act as a switch that hides or reveals numerous mutations throughout the genome, thus acting as an evolutionary capacitor. She proposed that a heat shock protein, hsp90, may act in the same way, normally preventing phenotypic consequences of genetic changes, but showing all changes at once when the HSP system is overloaded, either pharmacologically or under stressful environmental conditions.
Most of these variations are likely to be harmful, but a few unusual combinations may produce valuable new traits, spurring the pace of evolution. Cancer cells too have an extraordinary ability to evolve. Lindquist's lab investigates closely related evolutionary mechanisms involved in the progression of cancerous tumors and in the evolution of antibiotic-resistant fungi.
Lindquist made advances in nanotechnology, researching organic amyloid fibers capable of self-organizing into structures smaller than manufactured materials. Her group also developed a yeast "living test tube" model to study protein folding transitions in neurodegenerative diseases and to test therapeutic strategies through high-throughput screening.

Publications

Lindquist won numerous awards and honors including:
Lindquist was married to Edward Buckbee and had two daughters. She died of cancer in Boston at the age of 67 on October 27, 2016.