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Susan Lee Lindquist,
ForMemRS Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the Fellows of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural science, natural knowledge, incl ...
(June 5, 1949 – October 27, 2016) was an American professor of biology at
MIT The Massachusetts Institute of Technology (MIT) is a private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of modern technology and sc ...
specializing in
molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
, particularly the
protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...
problem within a family of molecules known as heat-shock proteins, and
prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...
s. Lindquist was a member and former director of the
Whitehead Institute Whitehead Institute for Biomedical Research is a non-profit research institute located in Cambridge, Massachusetts, United States that is dedicated to improving human health through basic biomedical research. It was founded as a fiscally indep ...
and was awarded the
National Medal of Science The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral science, behavior ...
in 2010.


Early life and education

Lindquist was born in Chicago, Illinois, to Iver and Eleanor (née Maggio), and attended
Maine South High School Maine South High School (officially known as Maine Township High School South) is a public four-year high school located in Park Ridge, Illinois, United States, a northwest suburb of Chicago. It is part of Maine Township High School District 207 ...
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 The University of Illinois Urbana-Champaign (UIUC, U of I, Illinois, or University of Illinois) is a public university, public land-grant university, land-grant research university in the Champaign–Urbana metropolitan area, Illinois, United ...
as an undergraduate and received her PhD in biology from
Harvard University Harvard University is a Private university, private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the History of the Puritans in North America, Puritan clergyma ...
in 1976. She completed a post-doctoral fellowship at the
American Cancer Society The American Cancer Society (ACS) is a nationwide non-profit organization dedicated to eliminating cancer. The ACS publishes the journals ''Cancer'', '' CA: A Cancer Journal for Clinicians'' and '' Cancer Cytopathology''. History The society w ...
.


Career

Upon completing her dissertation in 1976, Lindquist moved to the
University of Chicago The University of Chicago (UChicago, Chicago, or UChi) is a Private university, private research university in Chicago, Illinois, United States. Its main campus is in the Hyde Park, Chicago, Hyde Park neighborhood on Chicago's South Side, Chic ...
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 protein Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including ex ...
s in regulating the cellular response to environmental stresses. Lindquist pioneered the use of
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
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 The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...
in 1988. After making important new discoveries to prions, Lindquist moved to
MIT The Massachusetts Institute of Technology (MIT) is a private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of modern technology and sc ...
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 The Eli and Edythe L. Broad Institute of MIT and Harvard (IPA: , pronunciation respelling: ), often referred to as the Broad Institute, is a biomedical and genomic research center located in Cambridge, Massachusetts, United States. The institu ...
of MIT and
Harvard Harvard University is a private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher lear ...
, 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 (presented in 2010), 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 Leo Laporte (; born November 29, 1956) is the former host of ''The Tech Guy'' weekly radio show and founder of TWiT.tv, an Internet podcast network focusing on technology. He is also a former TechTV technology host (1998–2008) and a technology a ...
's
TWiT TWiT.tv is a podcast network that broadcasts technology-focused podcasts, founded by broadcaster and author Leo Laporte in 2005, and run by his wife and company CEO Lisa Laporte. The network began operation in April 2005 with the launch of ...
network. In 2007, she participated in the
World Economic Forum The World Economic Forum (WEF) is an international non-governmental organization, international advocacy non-governmental organization and think tank, based in Cologny, Canton of Geneva, Switzerland. It was founded on 24 January 1971 by German ...
in Davos, Switzerland with other MIT leaders. Lindquist also co-founded two companies to translate research into potential therapies, FoldRx and Yumanity Therapeutics (with N. Anthony Coles),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 companies developing drug therapies for diseases of protein misfolding and amyloidosis. In November 2016,
Johnson & Johnson Johnson & Johnson (J&J) is an American multinational pharmaceutical, biotechnology, and medical technologies corporation headquartered in New Brunswick, New Jersey, and publicly traded on the New York Stock Exchange. Its common stock is a c ...
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 Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
based upon the
inheritance Inheritance is the practice of receiving private property, titles, debts, entitlements, privileges, rights, and obligations upon the death of an individual. The rules of inheritance differ among societies and have changed over time. Offi ...
of
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s with new, self-perpetuating shapes rather than new
DNA sequence A nucleic acid sequence is a succession of bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five different letters that indicate the order of the nu ...
s. This research provided a
biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...
framework for understanding devastating neurological illnesses such as
Alzheimer's Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
,
Parkinson's Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalen ...
, Huntington's, and
Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD) is an incurable, always fatal neurodegenerative disease belonging to the transmissible spongiform encephalopathy (TSE) group. Early symptoms include memory problems, behavioral changes, poor coordination, visu ...
s. 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 disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
s, and an unusual type of inheritance in
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
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 Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and always fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of the ...
in
cattle Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
and Creutzfeldt–Jacob Disease in humans.
Lindquist worked on the PSI+ element in yeast (a
prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...
) and how it can act as a switch that hides or reveals numerous
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s throughout the
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
, thus acting as an evolutionary capacitor. She proposed that a
heat shock protein Heat shock proteins (HSPs) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including ex ...
,
hsp90 Hsp90 (heat shock protein 90) is a chaperone (protein), chaperone protein that assists other proteins to protein folding, fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of ...
, may act in the same way, normally preventing
phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
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 Nanotechnology is the manipulation of matter with at least one dimension sized from 1 to 100 nanometers (nm). At this scale, commonly known as the nanoscale, surface area and quantum mechanical effects become important in describing propertie ...
, 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

* * * * . * * * * * * * * * *


Awards and honors

Lindquist won numerous awards and honors including: * Elected to the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (The Academy) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and other ...
in 1996. * Elected to the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...
in 1997. * Named a fellow of the
American Academy of Microbiology American(s) may refer to: * American, something of, from, or related to the United States of America, commonly known as the "United States" or "America" ** Americans, citizens and nationals of the United States of America ** American ancestry, p ...
in 1997. * Received the
Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...
/Drew Award in Biomedical Research in 2000. * Received the Dickson Prize in Medicine in 2003. * Elected to the
American Philosophical Society The American Philosophical Society (APS) is an American scholarly organization and learned society founded in 1743 in Philadelphia that promotes knowledge in the humanities and natural sciences through research, professional meetings, publicat ...
in 2003. * Named one of the 50 most important women in science by ''Discover'' Magazine in 2002. * Awarded the
Sigma Xi Sigma Xi, The Scientific Research Honor Society () is an international non-profit honor society for scientists and engineers. Sigma Xi was founded at Cornell University by a faculty member and graduate students in 1886 and is one of the oldest ...
William Procter Prize for Scientific Achievement The William Procter Prize for Scientific Achievement is an award given by Sigma Xi, a scientific-research honor society. The Procter Prize is presented annually to a scientist who has made an outstanding contribution to scientific research and has d ...
in 2006. * Elected to the
Institute of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...
of the National Academies in 2006. * Awarded the
Genetics Society of America The Genetics Society of America (GSA) is a scholarly membership society of more than 5,500 genetics researchers and educators, established in 1931. The Society was formed from the reorganization of the Joint Genetics Sections of the American Soc ...
Medal in 2008. * Awarded the
Otto Warburg Medal The Otto Warburg Medal is awarded annually by the German Society for Biochemistry and Molecular Biology (German: ''Gesellschaft für Biochemie und Molekularbiologie'' or ''GBM'') to honour scientists who have contributed important work in the field ...
by the German Society for Biochemistry and Molecular Biology in 2008. * Awarded the
FASEB Excellence in Science Award The Excellence in Science Award was established by the Federation of American Societies for Experimental Biology (FASEB) in 1989 to recognize outstanding achievement by women in biological science. All women who are members of one or more of the so ...
in 2009. * Awarded the Max Delbrück Medal, Berlin, Germany, in 2010. * Awarded the Mendel Medal by
The Genetics Society The Genetics Society is a British learned society. It was founded by William Bateson and Edith Rebecca Saunders in 1919 and celebrated its centenary year in 2019. It is therefore one of the oldest learned societies devoted to genetics. Its membe ...
, UK, in 2010. * Awarded the
National Medal of Science The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral science, behavior ...
(for 2009) in 2010. * Made an Associate Member of the
European Molecular Biology Organization The European Molecular Biology Organization (EMBO) is a professional, non-profit organization of more than 2,100 life scientists. Its goal is to promote research in life science and enable international exchange between scientists. It co-funds cour ...
in 2011. * Awarded the E.B. Wilson Medal by The American Society for Cell Biology in 2012. * Awarded the
Vanderbilt University School of Medicine Vanderbilt University School of Medicine (VUSM) is the graduate medical school of Vanderbilt University, a private research university located in Nashville, Tennessee. The School of Medicine is primarily housed within the Eskind Biomedical Libra ...
Vanderbilt Prize for Women's Excellence in Science and Mentorship in 2014. * Elected a Foreign Member of the Royal Society (ForMemRS) in 2015. * Vallee Visiting Professorship (2015) * Awarded the Albany Medical Center Prize in Medicine and Biomedical Research with F. Ulrich Hartl and Arthur Horwich in 2016. * Awarded (posthumously) the Rosenstiel Award in 2016.


Personal life

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.


References

{{DEFAULTSORT:Lindquist, Susan 1949 births 2016 deaths American geneticists American molecular biologists American people of Italian descent American people of Swedish descent American cell biologists Deaths from cancer in Massachusetts Fellows of the American Academy of Arts and Sciences Foreign members of the Royal Society Harvard University alumni Howard Hughes Medical Investigators Massachusetts Institute of Technology School of Science faculty Members of the National Academy of Medicine Members of the United States National Academy of Sciences People from Park Ridge, Illinois University of Illinois Urbana-Champaign alumni Whitehead Institute faculty American women molecular biologists Members of the American Philosophical Society Biologists from Illinois