Lindquist's father and mother were of Swedish and Italian descent, respectively,[13] and although they expected her to become a housewife,[14] Susan studied microbiology at theUniversity of Illinois as an undergraduate and received her PhD in biology fromHarvard University in 1976.[15] She completed a post-doctoral fellowship at theAmerican Cancer Society.[16]
Upon completing her dissertation in 1976, Lindquist moved to theUniversity of Chicago for a short post-doc before being hired as a faculty member in the Biology Department in 1978,[17] becoming the Albert D. Lasker Professor of Medical Sciences with the founding of the Department of Molecular Genetics and Cell Biology in 1980.[16] At the University of Chicago Lindquist investigated the role ofheat shock proteins in regulating the cellular response to environmental stresses. Lindquist pioneered the use ofyeast 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 theHoward Hughes Medical Institute in 1988.[17] After making important new discoveries toprions, Lindquist moved toMIT in 2001 and was appointed as Director of theWhitehead Institute for Biomedical Research, one of the first women in the nation to lead a major independent research organization.[18]
Lindquist was awarded the National Medal of Science in 2009 (presented in 2010), for research contributions to protein folding.[20]
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 onLeo Laporte'sTWiT network.[21] In 2007, she participated in theWorld Economic Forum in Davos, Switzerland with other MIT leaders.[22]
Lindquist also co-founded two companies to translate research into potential therapies, FoldRx and Yumanity Therapeutics (withN. Anthony Coles),[23] 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]
Lindquist is best known for her research that provided strong evidence for a new paradigm ingenetics based upon theinheritance ofproteins with new, self-perpetuating shapes rather than newDNA sequences. This research provided abiochemical framework for understanding devastating neurological illnesses such asAlzheimer's,Parkinson's,Huntington's, andCreutzfeldt–Jakob diseases.[12] 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 withneurodegenerative diseases, and an unusual type of inheritance inyeast 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 asmad-cow disease incattle and Creutzfeldt–Jacob Disease in humans.[27]
Lindquist worked on the PSI+ element in yeast (aprion) and how it can act as a switch that hides or reveals numerousmutations throughout thegenome, thus acting as anevolutionary capacitor. She proposed that aheat shock protein,hsp90, may act in the same way, normally preventingphenotypic consequences of genetic changes, but showing all changes at once when the HSP system is overloaded, either pharmacologically or under stressful environmental conditions.[28]
Susan Lindquist
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 innanotechnology, 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.
^McKenzie, Susan Lee Lindquist (1976).Protein and RNA synthesis induced by heat treatment in Drosophila melanogaster tissue culture cells (PhD thesis). Harvard University.OCLC14767508.
