Lindquist's father and mother were of Swedish and Italian descent, respectively,[14] and although they expected her to become a housewife,[15] Susan studied microbiology at the
University of Illinois as an undergraduate and received her PhD in biology from
Harvard University in 1976.[16] She completed a post-doctoral fellowship at the
American Cancer Society.[17]
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,[18] becoming the Albert D. Lasker Professor of Medical Sciences with the founding of the Department of Molecular Genetics and Cell Biology in 1980.[17] 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.[18] 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.[19]
Lindquist was awarded the National Medal of Science in 2009 (presented in 2010), for research contributions to protein folding.[21]
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.[22] In 2007, she participated in the
World Economic Forum in Davos, Switzerland with other MIT leaders.[23]
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.[24][25]
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.[26]
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.[13] 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.[27]
Lindquist worked on the PSI+ element in yeast (a
prion) 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.[28]
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[29] and in the evolution of antibiotic-resistant fungi.[30]
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.[31]
Serio, T.; Cashikar, A.; Kowal, A.; Sawicki, G.; Moslehi, J.; Serpell, L.; Arnsdorf, M.; Lindquist, S. (2000). "Nucleated conformational conversion and the replication of conformational information by a prion determinant". Science. 289 (5483): 1317–1321.
Bibcode:
2000Sci...289.1317S.
doi:
10.1126/science.289.5483.1317.
PMID10958771.
^Parsell, D.A.; Lindquist, S. (1993). "The Function of Heat-Shock Proteins in Stress Tolerance: Degradation and Reactivation of Damaged Proteins". Annual Review of Genetics. 27: 437–96.
doi:
10.1146/annurev.ge.27.120193.002253.
PMID8122909.
S2CID31351089.
^McKenzie, Susan Lee Lindquist (1976). Protein and RNA synthesis induced by heat treatment in Drosophila melanogaster tissue culture cells (PhD thesis). Harvard University.
OCLC14767508.