Susan Lindquist in 2015, portrait via the Royal Society
|Born||Susan Lee Lindquist
June 5, 1949
Chicago, Illinois, U.S.
|Died||October 27, 2016(aged 67)|
|Thesis||Protein and RNA synthesis induced by heat treatment in Drosophila melanogaster tissue culture cells (1976)|
|Doctoral advisor||Matthew Meselson|
|Known for||protein folding
Susan Lee Lindquist (June 5, 1949 – October 27, 2016) was a 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.
Although expected to become a housewife by her parents, Lindquist studied microbiology at the University of Illinois as an undergraduate and received her PhD in biology from Harvard University in 1976.
Research and career
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 disease, Parkinson's, Huntington's, and Creutzfeldt–Jakob disease. She is 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 Creutzfeld–Jacob Disease in humans."
- --from "From Mad Cows to 'Psi-chotic' Yeast: A New Paradigm in Genetics," NAS Distinguished Leaders in Science Lecture Series, November 10, 1999.
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 also 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.
Recently,[when?] 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. She is a co-founder of FoldRx, a company developing drug therapies for diseases of protein misfolding and amyloidosis.
Dr. 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.
Dr. Lindquist served as a Professor at the University of Chicago for 23 years and then at MIT, where she taught concurrent with her Whitehead Institute appointment since 2001, and Investigator of the Howard Hughes Medical Institute.. She was the Albert D. Lasker Professor of Medical Sciences in the Department of Molecular Genetics and Cell Biology at the University of Chicago, and the Director of the Whitehead Institute for Biomedical Research from 2001-2004 - one of the first women in the nation to lead a major independent research organization. In 2004, she resumed her research focus 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.
- Jarosz, D. F.; Lindquist, S. (2010). "Hsp90 and Environmental Stress Transform the Adaptive Value of Natural Genetic Variation". Science. 330 (6012): 1820–1824. doi:10.1126/science.1195487. PMC . PMID 21205668.
- Alberti, S.; Halfmann, R.; King, O.; Kapila, A.; Lindquist, S. (2009). "A Systematic Survey Identifies Prions and Illuminates Sequence Features of Prionogenic Proteins". Cell. 137 (1): 146–158. doi:10.1016/j.cell.2009.02.044. PMC . PMID 19345193..
- Gitler, A. D.; Chesi, A.; Geddie, M. L.; Strathearn, K. E.; Hamamichi, S.; Hill, K. J.; Caldwell, K. A.; Caldwell, G. A.; Cooper, A. A.; Rochet, J. C.; Lindquist, S. (2009). "Α-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity". Nature Genetics. 41 (3): 308–315. doi:10.1038/ng.300. PMC . PMID 19182805.
- Dai, C.; Whitesell, L.; Rogers, A. B.; Lindquist, S. (2007). "Heat Shock Factor 1 is a Powerful Multifaceted Modifier of Carcinogenesis". Cell. 130 (6): 1005–1018. doi:10.1016/j.cell.2007.07.020. PMC . PMID 17889646.
- Cooper, A. A.; Gitler, A.; Cashikar, A.; Haynes, C.; Hill, K.; Bhullar, B.; Liu, K.; Xu, K.; Strathearn, K.; Liu, F.; Cao, S.; Caldwell, K. A.; Caldwell, G. A.; Marsischky, G.; Kolodner, R. D.; Labaer, J.; Rochet, J. C.; Bonini, N. M.; Lindquist, S. (2006). "-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models". Science. 313 (5785): 324–328. doi:10.1126/science.1129462. PMC . PMID 16794039.
- Cowen, L. E.; Lindquist, S. (2005). "Hsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi". Science. 309 (5744): 2185–2189. doi:10.1126/science.1118370. PMID 16195452.
- Krishnan, R.; Lindquist, S. L. (2005). "Structural insights into a yeast prion illuminate nucleation and strain diversity". Nature. 435 (7043): 765–772. doi:10.1038/nature03679. PMC . PMID 15944694.
- Si, K.; Lindquist, S.; Kandel, E. (2003). "A neuronal isoform of the aplysia CPEB has prion-like properties". Cell. 115 (7): 879–891. doi:10.1016/S0092-8674(03)01020-1. PMID 14697205.
- Queitsch, C.; Sangster, T. A.; Lindquist, S. (2002). "Hsp90 as a capacitor of phenotypic variation". Nature. 417 (6889): 618–624. doi:10.1038/nature749. PMID 12050657.
- 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. doi:10.1126/science.289.5483.1317. PMID 10958771.
- Patino, M. M.; Liu, J. -J.; Glover, J. R.; Lindquist, S. (1996). "Support for the Prion Hypothesis for Inheritance of a Phenotypic Trait in Yeast". Science. 273 (5275): 622–626. doi:10.1126/science.273.5275.622. PMID 8662547.
- Lindquist, S. (1981). "Regulation of protein synthesis during heat shock". Nature. 293 (5830): 311–314. doi:10.1038/293311a0. PMID 6792546.
Awards and honors
Lindquist has won numerous awards and honors including:
- Elected to the American Academy of Arts and Sciences in 1996.
- Elected to the National Academy of Sciences in 1997.
- Named a fellow of the American Academy of Microbiology in 1997.
- Named Albert D. Lasker Professor of Medical Sciences in 1999.
- Received the Novartis/Drew Award in Biomedical Research in 2000.
- Served as director of the Whitehead Institute for Biomedical Research from 2001-2004.
- Received the Dickson Prize in Medicine in 2002.
- Named one of the 50 most important women in science by Discover Magazine in 2002.
- Awarded the Sigma Xi William Procter Prize for Scientific Achievement in 2006.
- Elected to the Institute of Medicine of the National Academies in 2006.
- Awarded the Genetics Society of America Medal in 2008.
- Awarded the Otto Warburg Medal by the German Society for Biochemistry and Molecular Biology in 2008.
- Awarded the FASEB Excellence in Science Award in 2009.
- Awarded the Max Delbrück Medal, Berlin, Germany, in 2010.
- Awarded the Mendel Medal by The Genetics Society, UK, in 2010.
- Awarded the National Medal of Science (for 2009) in 2010.
- Awarded the E.B. Wilson Medal by The American Society for Cell Biology in 2012.
- Elected a Foreign Member of the Royal Society (ForMemRS) In 2015
- Awarded the 2016 Albany Medical Center Prize in Medicine and Biomedical Research with F. Ulrich Hartl and Arthur Horwich.
Lindquist was married to Edward Buckbee and has two adult daughters. She died of cancer at the age 67 on October 27, 2016.
- Gitschier, J. (2011). "A Flurry of Folding Problems: An Interview with Susan Lindquist". PLoS Genetics. 7 (5): e1002076. doi:10.1371/journal.pgen.1002076. PMC . PMID 21589898.
- Hopkins, N. (2008). "The 2008 Genetics Society of America Medal". Genetics. 178 (3): 1125–1128. doi:10.1534/genetics.104.017834. PMC . PMID 18385104.
- http://www.whitehead.mit.edu/research/faculty/lindquist.html Susan Lindquist Research Summary
- http://web.wi.mit.edu/lindquist/pub/ Lindquist Lab Website
- Kain, K. (2008). "Using yeast to understand protein folding diseases: An interview with Susan Lindquist". Disease Models and Mechanisms. 1 (1): 17–19. doi:10.1242/dmm.000810. PMC . PMID 19048046.
- Lindquist, S. (1986). "The Heat-Shock Response". Annual Review of Biochemistry. 55: 1151–1191. doi:10.1146/annurev.bi.55.070186.005443. PMID 2427013.
- 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: 437–496. doi:10.1146/annurev.ge.27.120193.002253. PMID 8122909.
- Susan Lindquist's seminars: "The Surprising World of Prion Biology"
- Video of Lindquist discussing her work, from the National Science & Technology Medals Foundation
- Gitschier, Jane. "A Flurry of Folding Problems: An Interview with Susan Lindquist". PLoS Genetics. 7 (5): e1002076. doi:10.1371/journal.pgen.1002076. PMC . PMID 21589898.
- McKenzie, Susan Lee Lindquist (1976). Protein and RNA synthesis induced by heat treatment in Drosophila melanogaster tissue culture cells (PhD thesis). Harvard University. OCLC 14767508.
- Valverde, Miriam (November 18, 2010). "Cambridge researcher honored at White House". The Boston Globe.
- "Whitehead Institute - News - 2016 - Susan Lindquist, accomplished and beloved scientist, has died at age 67". wi.mit.edu. Retrieved 2016-10-28.