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Nobel Prize 2009 in Physiology or Medicine (2)


Always look at what the organism is telling you 
  ( Carol Greider)
  Carol Greider  or Carolyn Widney (born April 15, 1961) is an American molecular biologist. She is Daniel Nathans Professor and Director of Molecular Biology and Genetics at Johns Hopkins University.[1] She discovered the enzyme telomerase in 1984, when she was a graduate student of Elizabeth Blackburn at the University of California, Berkeley. Greider pioneered research on the structure of telomeres, the ends of the chromosomes.

“I didn't want to do what everyone else was doing,” Carol W. Grieder
Carol W Greider grew up in Davis, CA, near the University of California, Davis campus, where her father Kenneth Greider  was a physics professor. While her high school classmates descended on the University of California, Davis, or nearby Berkeley for college, she decided to move down the coast to attend the University of California, Santa Barbara.. Originally interested in marine biology, she enrolled in the university's College of Creative Studies, whose small size meant its students could enjoy a high faculty-to-student ratio.

Carol W. Greider's mentor, a dynamic researcher named Bea Sweeney, insisted that she try out research right away, to find out whether hands-on science would suit her as much as textbook learning did. Greider sampled a few laboratories as a freshman, but, when she landed in a biochemistry laboratory the next year, she knew she had found her home. “You can't really know without being in a lab the style of science that it does,” she says. “But once you get into an environment that fits your own scientific way of thinking about problems, it just clicks.”
 
Carol W. Grieder stayed in the biochemistry laboratory for two and a half years, enjoying lively conversations with other laboratory members and the mechanistic flavor of thinking that pervaded. Even during her junior year abroad in Germany, she found a biochemistry laboratory in which to work. After this preview of graduate student life and research publishing responsibilities, the career path of an academic scientist still appealed to her. Greider applied to molecular biology graduate programs across California.
 
 
Her application package was a bit unusual, Greider says. “I had great research experience, great letters of recommendation, and outstanding grades, but I had poor GREs.” Although she did not know it growing up, Greider suffers from dyslexia, which affected her scores on standardized tests. Only two schools—the California Institute of Technology (Pasadena, CA) and the University of California, Berkeley— offered her an interview. When she met with cell biologist Elizabeth Blackburn in Berkeley, things clicked again. “I really liked my conversations with Liz, and there were a number of other people in the department that would be potentially fun to work with, so I went there,” says Greider.
Throughout the late 1970s and early 1980s, Blackburn and other researchers had found that telomeres show unusual behavior and structure. The chromosome caps consist of multiple repeats of a simple motif, which in the pond ciliate Tetrahymena was six nucleotides long. The mechanism by which these sequence repeats were added to the ends of telomeres in ciliates and yeast had not yet been identified. Most researchers believed recombination was responsible, but Blackburn favored the explanation of specific repeat addition by an as-yet-unknown enzyme. She decided that Tetrahymena, a pond ciliate with a macronucleus and 40,000 telomeres, was a natural place to look. When she started work in Black-burn's laboratory in April 1984, Greider set out to find this hypothetical enzyme in Tetrahymena.
We don’t know for any individual what this would mean ... There are no clinical studies that tell us anything about the other 99 percent  Carol W Greider
It was a tall order for a graduate student, but Greider was clearly up to the task, says Blackburn, now the Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at the University of California, San Francisco. “If you were easily intimidated, you wouldn't take on that kind of project,” Blackburn says. “We had to be both rigorous and enterprising, and those are exactly the characteristics that Carol has. The combination is a great strength.” For her part, Greider worked 12-hour days and supplemented her existing biochemistry knowledge with DNA cloning techniques and other skills needed for the project.
 
Nine months after she began the project, and after much trial and error finding the right substrate and assay, Greider identified the first signs of her enzyme. On Christmas Day in 1984, she developed one of her gels and saw a ladder of the characteristic Tetrahymena 6-base telomeric repeats—exactly the pattern that would be expected from a telomere-synthesizing enzyme. But she and Blackburn did not celebrate right away. Greider says, “When you find something that is really exciting that you think may be something new, the first things that go through your mind should be, `What else could it be? How could I be being fooled?”'
Many potential sources of artifacts existed, and Greider and Blackburn wanted to rule out as many as possible. In June 1985 came the persuasive experiment, which showed that yeast telomeres functioned in Tetrahymena and indicated that they were seeing a new enzyme activity. This time, Greider went home and celebrated. Publishing in December 1985, Greider and Blackburn originally called the newly discovered activity “Tetrahymena telomere terminal transferase” because it seemed to add telomere repeats in a manner similar to terminal transferase Deciding that this name was “a mouthful,” Greider says, they later shortened it to “telomerase.”

Over time, Carol W. Grieder became increasingly interested in the physiological effects of telomerase in mammals and how the biochemistry of mammalian telomerase differs from that of microorganisms. Her laboratory created a knockout mouse allowing them to address such questions “I decided to focus on the mouse and separate myself from [Geron] to some degree, so I could do the kinds of really academic studies I wanted to do,” Greider says.
In 1997, Carol W. Grieder and her husband, Nathaniel, a science historian, moved to Maryland to take on positions at neighboring universities. Her husband worked at The George Washington University in Washington, DC, while Greider accepted an associate professor position at The Johns Hopkins University School of Medicine in Baltimore, MD. It was a good move, she says, because she wanted to work with more graduate students. Cold Spring Harbor is “post-doc heavy,” she explains. “With all post-docs, there's a lot of pressure in terms of them getting a job and having their own territory. Graduate students are a little more open to trying different things. There's a different speed at which they learn.” Students now fill more than half her laboratory at Johns Hopkins. “I select for people that like to be very independent,” she says. “It's more like having a day-to-day collaboration with smart people, and I find that fun.”
Greider and her family live near the Homewood "faculty ghetto" of Johns Hopkins University. She and her husband have a son, Charles,

Carol Greider Awards, Honors:
 
Albert Lasker Award for Basic Medical Research 2006
The Wiley Prize in Biomedical Sciences 2006
Lila Gruber Cancer Research Award 2006
Fellow, American Academy of Microbiology 2004
Fellow, American Association for the Advancement of Science 2003
Member, National Academy of Sciences 2003
Fellow, American Academy of Arts and Sciences 2003
Richard Lounsbery Award (NAS) 2003
Harvey Society Lecture 2000
Rosenstiel Award in Basic Medical Research 1999
Passano Foundation Award 1999
Gairdner Foundation Award 1998
Ellison Medical Foundation Senior Scholar 1998
Schering-Plough Scientific Achievement Award, American Society for Biochemistry and Molecular Biology 1997
Cornelius Rhoads Award, American Association for Cancer Research 1996
Glenn Foundation Award, American Society for Cell Biology 1995
Gertrude Elion Cancer Research Award, American Association for Cancer Research 1994
Allied Signal Outstanding Project Award 1992
Pew Scholar in the Biomedical Sciences 1990-1994
Phi Beta Kappa Society 1983
Regents Scholarship, University of California 1981 

Carol Greider Reviews and Book Chapters: 
Greider, C.W. (2007) Telomerase RNA Levels Limit the Telomere Length Equilibrium. Cold Spring Harbor Laboratory Symposium on Quantitative Biology. Vol. LXXI 225-229.
. Blackburn, E. H., Greider, C. W., and Szostak, J. W. (2006). Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nat. Med. 12, 1133-1138.
. Chen, J.-L., and Greider, C. W. (2006). Telomerase Biochemistry and Biogenesis. In Telomeres, T. DeLange, E. H. Blackburn, and V. Lundblad, Cold Spring Harbor, NY, Cold Spring Harbor Press 49-73.
. Armanios, M., and Greider, C.W. (2005). Telomerase and Cancer Stem Cells. Cold Spring Harbor Laboratory Symposium on Quantitative Biology. Vol. LXX 205-208.
. Chen, J.L., and Greider, C.W. (2004). An emerging consensus for telomerase RNA structure. Proc. Natl. Acad. Sci. U.S.A. 101: 14683-14684.
. Chen, J.L., and Greider, C.W. (2004). Telomerase RNA structure and function: implications for dyskeratosis congentia Trends Biochem Sci. 29: 183-192.
. Greider, C.W., and Blackburn, E.H. (2004). Tracking Telomerase. Cell S11: S83-S86
Feldser, D. M., Hackett, J., and Greider, C. W. (2003). Telomere dysfunction and the initiation of genome instability. Nature Reviews Cancer 3: 623-627. 

. Hackett, J. A., and Greider, C. W. (2002). Balancing Instability: Dual roles for telomerase and telomere dysfunction in tumorigenesis, Oncogene, 21: 619-626
. Greider, C.W. 2001 Cellular responses to telomere shortening: cellular senescence as a tumor suppressor mechanism. Harvey Lect: 96: 33-50.

. Hemann, M. T., Hackett, J., IJpma, A., and Greider, C. W. (2000). Telomere length, telomere binding proteins and DNA damage signaling, Cold Spring Harbor Laboratory Symposium on Quantitative Biology LXV, 275-279.


. Kass-Eisler, A., and Greider, C.W. (2000). Recombination and telomere-length maintenance. Trends Biochem. Sci. 25: 200-204.
. Greider, C.W. (1999). Telomeres do D-loop-T-loop. Cell 97: 419-422.
. Greider, C.W. (1999). Telomerase Activation: one step on the road to cancer?. Trends Genet. 15: 109-11.
. Greider, C.W. (1998). Telomeres and senescence: the history, the experiment, the future. Curr. Biol. 8: R178-R181.
. Greider, C.W. (1998). Telomerase activity, cell proliferation and cancer. Proc. Natl. Acad. Sci. U.S.A. 95: 90-92.
Greider, C.W., K. Collins, C. Autexier. (1996). Telomerases. In: DNA replication in Eukaryotic Cells. M.L. DePamphlis, Ed. Cold Spring Harbor Laboratory Press. Cold Spring Harbor New York. pp 619-638.
. Greider, C.W., and Blackburn, E.H. (1996). Telomeres, telomerase and cancer. Scientific American 274: 80-85.
. Greider, C.W. (1996). Telomere length regulation. Ann. Rev. Biochem. 65: 337-365.
Greider, C. W., and Harley, C. B. (1996). Telomeres and telomerase in cell senescence and immortalization. In Cellular Aging and Cell Death, N. J. Holbrook, G. R. Martin, and R. A. Lockshin, eds. (New York, Wiley-Liss, Inc), pp. 123-138.
Greider, C.W. (1995). Telomerase biochemistry and regulation. In: Telomeres. E.H. Blackburn and C.W. Greider, Eds. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, New York. pp 35-68.
Greider, C.W. (1994). Mammalian telomere dynamics: healing, fragmentation, shortening and stabilization. Curr. Opin. Genet. and Dev., 4: 203-211.

. Harley, C.B., Kim, N.W., Prowse, K.R., Weinrich, S.L., Hirsch, K.S., West, M.D., Bacchetti, S., Hirte, H.W., Counter, C.M., Greider, C.W., Piatyszek, M.A., Wright, W.E., and Shay, J.W. (1994). Telomerase, cell immortality and cancer. Cold Spring Harbor Symp. Quant. Biol. 59: 307-315.

. Greider , C.W., Autexier, C., Avilion, A.A., Collins, K., Harrington, L.A., Mantell, L.L., Prowse, K.R., Smith, S.K., Allsopp, R.C., Counter, C.M., Vaziri, H., Bacchetti, S., Harley, C.B. (1993). Telomeres and telomerase: biochemistry and regulation in senescence and immortalization. In: The Chromosome. J.S. Hesslop-Harrison and R.B. Flavell, eds. Bios Scientific Publishers Ltd. pp. 115-125.
. Greider, C.W. (1993). Telomerase and telomere length regulation: lessons from small eukaryotes to mammals. Cold Spring Harbor Symp. Quant. Biol. 58: 719-723.
. Greider, C.W. (1992). Telomere chromatin and gene expression. Curr. Biol. 2: 62–64.

. Greider, C.W. (1992). Telomeres and telomerase in small eukaryotes. In: The eukaryotic genome: organization and regulation. P.M.A. Broda, S.G. Oliver and P.F.G Sims, eds. Society for General Microbiology Symposium 50. Cambridge University Press. pp 31-42.

. Greider, C.W. (1991). Chromosome first aid. Cell 67: 645–647.
. Greider, C.W. (1991). Telomeres. Curr. Opin. Cell Biol. 3: 444–451.

3. Greider, C.W. (1990). Telomeres, telomerase and senescence. BioEssays 12: 363–369.
. Blackburn, E.H., Greider, C.W., Henderson, E., Lee, M., Shampay, J., and Shippen-Lentz, D. (1989). Recognition and elongation of telomeres by telomerase. Genome 31: 553–560.
. Henderson, E., Larson, D., Melton, W., Shampay, J., Spangler, E., Greider, C.W., Ryan, T., and Blackburn, E.H. Structure, synthesis and regulation of telomeres. (1988) In: Cancer Cells 6: Eukaryotic DNA Replication. Cold Spring Harbor Laboratory. vol 6: 453–461.
 

sources
http://www.greiderlab.org
http://www.hopkinsmedicine.org
http://www.daylife.com
http://www.ascb.org Biography of Carol W. Greider by Regina Nuzzo , Science Writer