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Susan Lindquist

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Susan Lindquist
Susan Lindquist in 2015, portrait via the Royal Society
Born
Susan Lee Lindquist

(1949-06-05)June 5, 1949
Chicago, Illinois, U.S.
DiedOctober 27, 2016(2016-10-27) (aged 67)
Boston, Massachusetts, U.S.
Alma mater
Known forprotein folding
heat-shock proteins
prions
Awards
Scientific career
FieldsMolecular biology
Institutions
ThesisProtein and RNA synthesis induced by heat treatment in Drosophila melanogaster tissue culture cells (1976)
Doctoral advisorMatthew Meselson[3]
Websitelindquistlab.wi.mit.edu

Susan Lee Lindquist, ForMemRS (June 5, 1949 – October 27, 2016) was an American professor of biology at MIT[4][5] specializing in molecular biology, particularly the protein folding problem[3][6] within a family of molecules known as heat-shock proteins,[7][8] and prions.[9] Lindquist was a member and former director of the Whitehead Institute and was awarded the National Medal of Science in 2010.[10][11][12]

Early life and education

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Lindquist was born in Chicago, Illinois, to Iver and Eleanor (née Maggio), and attended Maine South High School in Park Ridge.[13]

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

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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]

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.[20]

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 and Yumanity Therapeutics (with N. Anthony Coles),[24] companies developing drug therapies for diseases of protein misfolding and amyloidosis.[25][26]

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.[27]

Research

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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.[28]

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.[29]

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[30] and in the evolution of antibiotic-resistant fungi.[31]

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.[32]

Publications

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Awards and honors

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Lindquist won numerous awards and honors including:

Personal life

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Lindquist was married to Edward Buckbee and had two daughters.[20] She died of cancer in Boston at the age of 67 on October 27, 2016.[48][9]

References

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  1. ^ a b Hopkins, N. (2008). "The 2008 Genetics Society of America Medal". Genetics. 178 (3): 1125–1128. doi:10.1534/genetics.104.017834. PMC 2278094. PMID 18385104.
  2. ^ a b "Susan Lindquist". Royal Society. Retrieved October 30, 2016.
  3. ^ a b 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 3093363. PMID 21589898.
  4. ^ "Whitehead Institute – Faculty". Whitehead.mit.edu. Retrieved October 30, 2016.
  5. ^ "Lindquist Lab | Lindquist Lab at the Whitehead Institute for Biomedical Research | Lindquist Lab". mit.edu. February 10, 2016. Archived from the original on July 16, 2012. Retrieved October 30, 2016.
  6. ^ 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 2561974. PMID 19048046.
  7. ^ Lindquist, S. (1986). "The Heat-Shock Response". Annual Review of Biochemistry. 55: 1151–91. doi:10.1146/annurev.bi.55.070186.005443. PMID 2427013. S2CID 42450279.
  8. ^ 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. PMID 8122909. S2CID 31351089.
  9. ^ a b Whitesell, Luke; Santagata, Sandro (2016). "Susan Lindquist (1949–2016)". Science. 354 (6315): 974. Bibcode:2016Sci...354..974W. doi:10.1126/science.aal3609. ISSN 0036-8075. PMID 27884995. S2CID 5375718.
  10. ^ "Prions and Protein Folding: Video talk by Dr. Susan Lindquist". Ibiology.org. June 16, 2015. Archived from the original on October 29, 2016. Retrieved October 30, 2016.
  11. ^ "Whitehead Institute – Faculty". mit.edu. Retrieved October 30, 2016.
  12. ^ "Susan Lindquist – 2009 National Medal of Science". YouTube. November 29, 2010. Archived from the original on December 11, 2021. Retrieved October 30, 2016.
  13. ^ a b c d Grimes, William (October 28, 2016). "Susan Lindquist, Scientist Who Made Genetic Discoveries Using Yeast, Dies at 67". The New York Times. ISSN 0362-4331. Retrieved October 30, 2016.
  14. ^ Fleischman, John (October 28, 2016). "In Memoriam: Susan Lindquist, 67, Pioneer in Protein Folding Research – ASCB". ASCB Post. Archived from the original on November 3, 2016.
  15. ^ Gitschier, Jane (2011). "A Flurry of Folding Problems: An Interview with Susan Lindquist". PLOS Genetics. 7 (5): e1002076. doi:10.1371/journal.pgen.1002076. PMC 3093363. PMID 21589898.
  16. ^ 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.
  17. ^ a b c "FASEB ANNOUNCES RECIPIENT OF THE 2009 EXCELLENCE IN SCIENCE AWARD" (PDF). Federation of American Societies for Experimental Biology. July 18, 2008. Archived from the original (PDF) on June 30, 2014. Retrieved October 31, 2016.
  18. ^ a b c Fuchs, Elaine (December 2016). "Susan Lee Lindquist (1949–2016)". Cell. 167 (6): 1440–1442. Bibcode:2016Natur.540...40S. doi:10.1016/j.cell.2016.11.030. ISSN 0092-8674. PMID 29413691.
  19. ^ "Susan Lindquist, PhD". HHMI.org. Retrieved October 30, 2016.
  20. ^ a b "Whitehead Institute – News – 2016 – Susan Lindquist, accomplished and beloved scientist, has died at age 67". wi.mit.edu. October 28, 2016. Retrieved October 28, 2016.
  21. ^ "The President's National Medal of Science: Recipient Details | NSF – National Science Foundation". www.nsf.gov. Retrieved August 7, 2018.
  22. ^ "Futures in Biotech 1 Dr. Susan Lindquist | TWiT.TV". TWiT.tv. Retrieved October 31, 2016.
  23. ^ Yossi Sheffi. "MIT and the World Economic Forum". mit.edu. Retrieved October 30, 2016.
  24. ^ Carroll, John. UPDATED: Onyx vet Tony Coles embarks on a new biotech adventure. Fierce BioTech. December 15, 2014. https://www.fiercebiotech.com/biotech/updated-onyx-vet-tony-coles-embarks-on-a-new-biotech-adventure
  25. ^ "Scientific Founders – FoldRx". Archived from the original on July 11, 2011. Retrieved October 31, 2016.
  26. ^ "Yumanity Therapeutics". www.yumanity.com. Retrieved July 2, 2017.
  27. ^ WEISMAN, ROBERT (November 17, 2016). "A chair at MIT in Lindquist's memory". Boston Globe. Retrieved September 21, 2017.
  28. ^ "From Mad Cows to 'Psi-chotic' Yeast: A New Paradigm in Genetics", NAS Distinguished Leaders in Science Lecture Series, November 10, 1999.
  29. ^ "Susan Lindquist profile". MIT Biology. Archived from the original on October 30, 2016. Retrieved October 30, 2016.
  30. ^ "Whitehead Institute – News – 2014 – Master heat-shock factor supports reprogramming of normal cells to enable tumor growth and metastasis". wi.mit.edu. July 31, 2014. Retrieved October 31, 2016.
  31. ^ Heitman, Joseph (September 30, 2005). "A Fungal Achilles' Heel". Science. 309 (5744): 2175–2176. doi:10.1126/science.1119321. ISSN 0036-8075. PMID 16195450. S2CID 27186932.
  32. ^ a b "Whitehead Institute – News – 2016 – Whitehead's Susan Lindquist to receive prestigious Albany Prize in Medicine". wi.mit.edu. August 3, 2016. Retrieved October 31, 2016.
  33. ^ "Navigation for iFrame". accounts.asm.org. Retrieved October 31, 2016.
  34. ^ Webteam, University of Pittsburgh University Marketing Communications. "Susan L. Lindquist, PhD | Dickson Prize in Medicine". www.dicksonprize.pitt.edu. Retrieved October 30, 2016.
  35. ^ "Susan Lindquist, pioneering biologist and former director of Whitehead Institute, dies at 67 Biology professor and mentor to many investigated protein folding and its role in disease". MIT News. October 28, 2016. Retrieved May 1, 2019.
  36. ^ Svitil, Kathy (November 13, 2002). "The 50 Most Important Women in Science". Discover. Retrieved May 1, 2019.
  37. ^ a b "Susan L. Lindquist profile". jnj.com. Retrieved October 31, 2016.
  38. ^ "U.S. Scientist Receives Otto Warburg Medal Sponsored By QIAGEN". www.abnnewswire.net. Retrieved October 31, 2016.
  39. ^ "Professor Susan Lindquist from the Whitehead Institute Receives Max Delbrück Medal in Berlin". Mdc-berlin.de. Archived from the original on January 3, 2011. Retrieved October 30, 2016.
  40. ^ "2010 Mendel Lecture – The Genetics Society". Archived from the original on August 13, 2011. Retrieved October 31, 2016.
  41. ^ Valverde, Miriam (November 18, 2010). "Cambridge researcher honored at White House". The Boston Globe.
  42. ^ "Recipients of European Molecular Biology Organization Associate Member award". biology.mit.edu. Archived from the original on October 30, 2016. Retrieved October 30, 2016.
  43. ^ "Recipients of American Society for Cell Biology E.B. Wilson Medal award | MIT Biology". biology.mit.edu. Archived from the original on October 30, 2016. Retrieved October 30, 2016.
  44. ^ "Recipients of Vanderbilt University School of Medicine Vanderbilt Prize for Women's Excellence in Science and Mentorship award". biology.mit.edu. Archived from the original on October 30, 2016. Retrieved October 30, 2016.
  45. ^ "Fellows Directory". Royal Society. Retrieved October 30, 2016.
  46. ^ "2015 Vallee Visiting Professors Announced". The Vallee Foundation. 2014. Retrieved May 1, 2019.
  47. ^ "Current Winner – Rosenstiel Award – Rosenstiel Basic Medical Sciences Research Center – Brandeis University". www.brandeis.edu.
  48. ^ Grimes, William (October 29, 2016). "Susan Lindquist Scientist Who Made Genetic Discoveries Using Yeast Dies at 67". The New York Times. Retrieved October 30, 2016.
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