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Carol W. Greider

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Carol W. Greider
Greider in 2021
Born
Carolyn Widney Greider

(1961-04-15)April 15, 1961(age 63)
San Diego, California,U.S.
EducationUniversity of California, Santa Barbara(BA)
University of Göttingen
University of California, Berkeley(PhD)
Known forDiscovery oftelomerase
Spouse
​
​
(m.1993;div.2011)​
Children2
AwardsRichard Lounsbery Award(2003)
Lasker Award(2006)
Louisa Gross Horwitz Prize(2007)
Nobel Prize in Physiology or Medicine(2009)
Scientific career
FieldsMolecular biology
InstitutionsCold Spring Harbor Laboratory
Johns Hopkins School of Medicine
University of California, Santa Cruz
ThesisIdentification of a specific telomere terminal transferase activity in Tetrahymena extracts(1985)
Doctoral advisorElizabeth Blackburn
Other academic advisorsBeatrice M. Sweeney
David J. Asai
Leslie Wilson

Carolyn Widney Greider(born April 15, 1961) is an Americanmolecular biologistand Nobel laureate. She joinedthe University of California, Santa Cruzas a Distinguished Professor in the department ofmolecular,cell,anddevelopmental biology[1]in October 2020.

Greider discovered theenzymetelomerasein 1984, while she was a graduate student ofElizabeth Blackburnat theUniversity of California, Berkeley.Greider pioneered research on the structure oftelomeres,the ends of thechromosomes.She was awarded the 2009Nobel Prize for Physiology or Medicine,along with Blackburn andJack W. Szostak,for their discovery that telomeres are protected from progressive shortening by the enzymetelomerase.[2]

Early life and education[edit]

Greider was born inSan Diego,California.[3]Her father, Kenneth Greider, was aphysicsprofessor.[4]Her family moved from San Diego toDavis, California,where she spent many of her early years and graduated fromDavis Senior High Schoolin 1979. She graduated from theCollege of Creative Studiesat theUniversity of California, Santa Barbara,with aB.A.inbiologyin 1983. During this time she also studied at theUniversity of Göttingenand made significant discoveries there.[5]

Greider isdyslexicand states that her "compensatory skills also played a role in my success as a scientist because one has to intuit many different things that are going on at the same time and apply those to a particular problem".[6]Greider initially suspected her dyslexia after seeing patterns of common mistakes such as backward words when she received back graded work in the first grade.[7]Greider started to memorize words and their spellings rather than attempting to sound out the spelling of words.[6]Greider has worked significantly to overcome her dyslexia to become successful in her professional life and credits her dyslexia as helping her appreciate differences and making unusual decisions such as the one to work withTetrahymena,an unusual organism.[6]

Greider initially had difficulty getting into graduate school because of her lowGREscores, a result of her dyslexia. Greider applied to thirteen grad schools and was accepted to only two,California Institute of Technologyand theUniversity of California, Berkeley.[6]She chose to study at Berkeley.[6]

Discovery of telomerase[edit]

Greider completed her Ph.D. inmolecular biologyin 1987 atBerkeleyunderElizabeth Blackburn.While at Berkeley, Greider and Blackburn discovered how chromosomes are protected bytelomeresand the enzymetelomerase.[8] Greider joined Blackburn's laboratory in April 1984 looking for the enzyme that was hypothesized to add extraDNA basesto the ends ofchromosomes.Without the extra bases, which are added as repeats of a six-base pair motif, chromosomes are shortened duringDNA replication,eventually resulting in chromosome deterioration andsenescenceor cancer-causing chromosome fusion. Blackburn and Greider looked for the enzyme in the model organismTetrahymena thermophila,a fresh-waterprotozoanwith a large number of telomeres.[9]

On December 25, 1984, Greider first obtained results indicating that a particular enzyme was likely responsible. After six months of additional research, Greider and Blackburn concluded that it was the enzyme responsible for telomere addition. They published their findings in the journalCellin December 1985.[10]The enzyme, originally called "telomere terminal transferase," is now known as telomerase. Telomerase rebuilds the tips of chromosomes and determines the life span of cells.[11]

Greider's additional research to confirm her discovery was largely focused on identifying the mechanism that telomerase uses for elongation.[12]Greider chose to useRNAdegrading enzymes and saw that the telomeres stopped extending, which was an indication that RNA was involved in the enzyme.[12]

Subsequent career[edit]

Greider then started her own laboratory as a Cold Spring Harbor Laboratory Fellow, and also held a faculty position, at theCold Spring Harbor Laboratory,Long Island, New York.Greider continued to studyTetrahymenatelomerase, cloning the gene encoding the RNA component and demonstrating that it provided the template for the TTGGGG telomere repeats (1989)[13]as well as establishing that telomerase is processive (1991).[14]She was also able to reconstituteTetrahymenatelomerasein vitro(1994)[15]and define the mechanisms of template utilization (1995).[16]Greider also worked with Calvin Harley to show that telomere shortening underlies cellular senescence (1990).[17][18]To further test this idea mouse and human telomerase were characterized (1993)[19](1995)[20]and the mouse telomerase RNA component was cloned (1995).[21]

During this time, Greider, in collaboration withRonald A. DePinho,produced the first telomeraseknockout mouse,[22]showing that although telomerase is dispensable for life, increasingly short telomeres result in various deleteriousphenotypes,colloquially referred to as premature aging.[23]In the mid-1990s, Greider was recruited byMichael D. West,founder of biotechnology companyGeron(now CEO ofAgeX Therapeutics) to join the company's Scientific Advisory Board[24]and remained on the Board until 1997.

Greider accepted a faculty position at theJohns Hopkins University School of Medicinein 1997. Greider continued to study telomerase deficient mice and saw that her sixth generation of mice had become entirely sterile,[25]but when mated with control mice the telomerase deficient mice were able to regenerate theirtelomeres.[12][26]Greider continued to work on telomerase biochemistry, defining the secondary structure (2000)[27]and template boundary (2003)[28]of vertebrate telomerase RNA as well as analyzing the pseudoknot structure in human telomerase RNA (2005).[29]In addition to working inTetrahymenaand mammalian systems, Greider also studied telomeres and telomerase in the yeastSaccharomyces cerevisiae,further characterizing the recombination-based gene conversion mechanism that yeast cells null for telomerase use to maintain telomeres (1999)[30](2001).[31]Greider also showed that short telomeres elicit a DNA damage response in yeast (2003).[32]

Greider, Blackburn, and Szostak shared the 2006Albert Lasker Award for Basic Medical Researchfor their work on telomeres,[33]before jointly receiving theNobel Prizein 2009.

In February 2014, Greider was named aBloomberg Distinguished ProfessoratJohns Hopkins University.[34]

Greider served as director of and professor at the Department of Molecular Biology and Genetics atJohns Hopkins Medicine.[11]Greider was first promoted to Daniel Nathans Professor at the Department of Molecular Biology and Genetics in 2004.[35]

As of 2021, she is a professor of molecular, cellular, and developmental biology at UCSC.[citation needed]

Greider's lab employs both student and post-doctoral trainees[36]to further examine the relationships between the biology of telomeres and their connection to disease.[35]Greider's lab uses a variety of tools includingyeast,mice,and biochemistry to look at progressive telomere shortening.[37]Greider's lab is also researching howtumorreformation can be controlled by the presence of short telomeres.[37]The lab's future work will focus more on identifying the processing and regulation of telomeres and telomere elongation.[37]

Personal life[edit]

Greider marriedNathaniel C. Comfort,a fellow academic, in 1992. They divorced in 2011. She has two children.[38]

Awards and honors[edit]

Selected works[edit]

  • Greider, C. W. & Blackburn, E. H. (1985)."Identification of a specific telomere terminal transferase activity in Tetrahymena extracts".Cell.43(2 Pt. 1): 405–413.doi:10.1016/0092-8674(85)90170-9.PMID3907856.
  • Greider, C. W. & Blackburn, E. H. (1996). "Telomeres, Telomerase and Cancer".Scientific American.274(2): 92–97.Bibcode:1996SciAm.274b..92G.doi:10.1038/scientificamerican0296-92.PMID8560215.

See also[edit]

References[edit]

  1. ^Stephens, Tim."Eminent biologist Carol Greider to join UC Santa Cruz faculty".UC Santa Cruz News.RetrievedMay 22,2020.
  2. ^"Blackburn, Greider, and Szostak share Nobel".Dolan DNA Learning Center.Archived fromthe originalon October 22, 2009.RetrievedOctober 5,2009.
  3. ^Hopkins "Telomere" expert Carol Greider shares Germany's largest science prize
  4. ^"Former Davis resident receives Nobel Prize".The California Aggie.October 12, 2009.RetrievedApril 7,2015.
  5. ^Press release,University of Göttingen (December 9, 2009). (German)
  6. ^abcdeKathy Crockett."Carol Greider, Scientist, Nobel Prize Winner".Yale University.The Yale Center for Dyslexia & Creativity.RetrievedMarch 5,2015.
  7. ^"Carol W. Greider – Biographical".nobelprize.org.RetrievedSeptember 28,2017.
  8. ^"The Nobel Prize in Physiology or Medicine 2009".RetrievedApril 7,2015.
  9. ^Nuzzo, R.(2005)."Biography of Carol W. Greider".Proceedings of the National Academy of Sciences of the United States of America.102(23): 8077–8079.Bibcode:2005PNAS..102.8077N.doi:10.1073/pnas.0503019102.PMC1149435.PMID15928079.
  10. ^Greider, C. W.; Blackburn, E. H. (1985)."Identification of a specific telomere terminal transferase activity in Tetrahymena extracts".Cell.43(2 Pt 1): 405–413.doi:10.1016/0092-8674(85)90170-9.PMID3907856.
  11. ^ab"Carol Greider, Ph.D."Johns Hopkins Medicine – Research – Awards – Nobel.Archived fromthe originalon August 28, 2015.RetrievedApril 7,2015.
  12. ^abcAicher, Toby (March 18, 2015)."Science Spotlight: Nobel Laureate Carol Greider".The Middlebury Campus.RetrievedJanuary 24,2020.
  13. ^Greider, Carol W.; Blackburn, Elizabeth H. (January 1989). "A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis".Nature.337(6205): 331–337.Bibcode:1989Natur.337..331G.doi:10.1038/337331a0.PMID2463488.S2CID29191852.
  14. ^Greider, C W (September 1991)."Telomerase is processive".Molecular and Cellular Biology.11(9): 4572–4580.doi:10.1128/MCB.11.9.4572.PMC361337.PMID1875940.
  15. ^Autexier, C; Greider, C W (March 1, 1994)."Functional reconstitution of wild-type and mutant Tetrahymena telomerase".Genes & Development.8(5): 563–575.doi:10.1101/gad.8.5.563.PMID7523243.
  16. ^Autexier, C; Greider, C W (September 15, 1995)."Boundary elements of the Tetrahymena telomerase RNA template and alignment domains".Genes & Development.9(18): 2227–2239.doi:10.1101/gad.9.18.2227.PMID7557377.
  17. ^Greider, Carol W. (August 1990)."Telomeres, telomerase and senescence".BioEssays.12(8): 363–369.doi:10.1002/bies.950120803.PMID2241933.S2CID11920124.
  18. ^Harley, Calvin B.; Futcher, A. Bruce; Greider, Carol W. (May 1990). "Telomeres shorten during ageing of human fibroblasts".Nature.345(6274): 458–460.Bibcode:1990Natur.345..458H.doi:10.1038/345458a0.PMID2342578.S2CID1145492.
  19. ^Prowse, K. R.; Avilion, A. A.; Greider, C. W. (February 15, 1993)."Identification of a nonprocessive telomerase activity from mouse cells".Proceedings of the National Academy of Sciences.90(4): 1493–1497.Bibcode:1993PNAS...90.1493P.doi:10.1073/pnas.90.4.1493.PMC45900.PMID8434010.
  20. ^Feng, J.; Funk, W.; Wang, S.; Weinrich, S.; Avilion, A.; Chiu, C.; Adams, R.; Chang, E.; Allsopp, R.; Yu, J.; al., e. (September 1, 1995). "The RNA component of human telomerase".Science.269(5228): 1236–1241.Bibcode:1995Sci...269.1236F.doi:10.1126/science.7544491.PMID7544491.S2CID9440710.
  21. ^Blasco, M.; Funk, W.; Villeponteau, B.; Greider, C. (September 1, 1995). "Functional characterization and developmental regulation of mouse telomerase RNA".Science.269(5228): 1267–1270.Bibcode:1995Sci...269.1267B.doi:10.1126/science.7544492.PMID7544492.S2CID1315745.
  22. ^Blasco, María A; Lee, Han-Woong; Hande, M.Prakash; Samper, Enrique; Lansdorp, Peter M; DePinho, Ronald A; Greider, Carol W (October 1997)."Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA".Cell.91(1): 25–34.doi:10.1016/s0092-8674(01)80006-4.PMID9335332.S2CID13366934.
  23. ^Rudolph, Karl Lenhard; Chang, Sandy; Lee, Han-Woong; Blasco, Maria; Gottlieb, Geoffrey J; Greider, Carol; DePinho, Ronald A (March 1999)."Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice".Cell.96(5): 701–712.doi:10.1016/s0092-8674(00)80580-2.PMID10089885.S2CID11991355.
  24. ^"Geron Corporation 10K 1996".
  25. ^Lee, Han-Woong; Blasco, Maria A.; Gottlieb, Geoffrey J.; Horner, James W.; Greider, Carol W.; DePinho, Ronald A. (April 1998). "Essential role of mouse telomerase in highly proliferative organs".Nature.392(6676): 569–574.Bibcode:1998Natur.392..569L.doi:10.1038/33345.PMID9560153.S2CID4385788.
  26. ^Hemann, Michael T; Strong, Margaret A; Hao, Ling-Yang; Greider, Carol W (October 2001)."The Shortest Telomere, Not Average Telomere Length, Is Critical for Cell Viability and Chromosome Stability".Cell.107(1): 67–77.doi:10.1016/s0092-8674(01)00504-9.PMID11595186.S2CID10719526.
  27. ^Chen, Jiunn-Liang; Blasco, Maria A; Greider, Carol W (March 2000)."Secondary Structure of Vertebrate Telomerase RNA".Cell.100(5): 503–514.doi:10.1016/s0092-8674(00)80687-x.PMID10721988.S2CID15642776.
  28. ^Chen, J.-L. (November 15, 2003)."Template boundary definition in mammalian telomerase".Genes & Development.17(22): 2747–2752.doi:10.1101/gad.1140303.PMC280623.PMID14630939.
  29. ^Chen, J.-L.; Greider, C. W. (April 22, 2005)."Functional analysis of the pseudoknot structure in human telomerase RNA".Proceedings of the National Academy of Sciences.102(23): 8080–8085.Bibcode:2005PNAS..102.8080C.doi:10.1073/pnas.0502259102.PMC1149427.PMID15849264.
  30. ^Le, S; Moore, JK; Haber, JE; Greider, CW (May 1999)."RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase".Genetics.152(1): 143–52.doi:10.1093/genetics/152.1.143.PMC1460580.PMID10224249.
  31. ^Chen, Q.; Ijpma, A.; Greider, C. W. (March 1, 2001)."Two Survivor Pathways That Allow Growth in the Absence of Telomerase Are Generated by Distinct Telomere Recombination Events".Molecular and Cellular Biology.21(5): 1819–1827.doi:10.1128/MCB.21.5.1819-1827.2001.PMC86745.PMID11238918.
  32. ^IJpma, Arne S.; Greider, Carol W.; Koshland, Douglas (March 2003)."Short Telomeres Induce a DNA Damage Response in".Molecular Biology of the Cell.14(3): 987–1001.doi:10.1091/mbc.02-04-0057.PMC151574.PMID12631718.
  33. ^""Telomere" Expert Carol Greider Shares 2009 Nobel Prize in Physiology or Medicine ".Johns Hopkins University.RetrievedMarch 13,2015.
  34. ^Brooks, Kelly (February 17, 2014)."With Bloomberg Distinguished Professorships, Johns Hopkins aims to foster cross-specialty collaboration".Hub.Johns Hopkins University.RetrievedMarch 12,2015.
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  45. ^"Greider, Carol W."National Academy of Sciences.RetrievedJune 9,2011.
  46. ^NAS OnlineArchivedDecember 9, 2006, at theWayback Machine( "For her pioneering biochemical and genetic studies of telomerase, the enzyme that maintains the ends of chromosomes in eukaryotic cells." )
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Further reading[edit]

External links[edit]

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