Carol W. Greider | |
---|---|
Born | Carolyn Widney Greider April 15, 1961 San Diego, California, U.S. |
Education | University of California, Santa Barbara (BA) University of Göttingen University of California, Berkeley (PhD) |
Known for | Discovery of telomerase |
Spouse | |
Children | 2 |
Awards | Richard Lounsbery Award (2003) Lasker Award (2006) Louisa Gross Horwitz Prize (2007) Nobel Prize in Physiology or Medicine (2009) |
Scientific career | |
Fields | Molecular biology |
Institutions | Cold Spring Harbor Laboratory Johns Hopkins School of Medicine University of California, Santa Cruz |
Thesis | Identification of a specific telomere terminal transferase activity in Tetrahymena extracts (1985) |
Doctoral advisor | Elizabeth Blackburn |
Other academic advisors | Beatrice M. Sweeney David J. Asai Leslie Wilson |
Carolyn Widney Greider (born April 15, 1961) is an American molecular biologist and Nobel laureate. She is a Distinguished Professor of Molecular, Cell, and Developmental Biology [1] at the University of California, Santa Cruz.
Greider discovered the enzyme telomerase in 1984, while 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. She was awarded the 2009 Nobel Prize for Physiology or Medicine, along with Blackburn and Jack W. Szostak, for their discovery that telomeres are protected from progressive shortening by the enzyme telomerase. [2]
Greider was born in San Diego, California. [3] Her father, Kenneth Greider, was a physics professor. [4] Her family moved from San Diego to Davis, California, where she spent many of her early years and graduated from Davis Senior High School in 1979. She graduated from the College of Creative Studies at the University of California, Santa Barbara, with a B.A. in biology in 1983. During this time she also studied at the University of Göttingen and made significant discoveries there. [5]
Greider is dyslexic and 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 with Tetrahymena , an unusual organism. [6]
Greider initially had difficulty getting into graduate school because of her low GRE scores due to her dyslexia. Greider applied to thirteen grad schools and was accepted to only two, California Institute of Technology and the University of California, Berkeley. [6] She chose to study at Berkeley. [6]
Greider completed her Ph.D. in molecular biology in 1987 at Berkeley under Elizabeth Blackburn. While at Berkeley, Greider and Blackburn discovered how chromosomes are protected by telomeres and the enzyme telomerase. [8] Greider joined Blackburn's laboratory in April 1984 looking for the enzyme that was hypothesized to add extra DNA bases to the ends of chromosomes. Without the extra bases, which are added as repeats of a six-base pair motif, chromosomes are shortened during DNA replication, eventually resulting in chromosome deterioration and senescence or cancer-causing chromosome fusion. Blackburn and Greider looked for the enzyme in the model organism Tetrahymena thermophila , a fresh-water protozoan with a large number of telomeres. [9]
On December 25, 1984, Greider 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 journal Cell in 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 use RNA degrading enzymes and saw that the telomeres stopped extending, which was an indication that RNA was involved in the enzyme. [12]
Greider then started her laboratory as a Cold Spring Harbor Laboratory Fellow, and also held a faculty position, at the Cold Spring Harbor Laboratory, Long Island, New York. Greider continued to study Tetrahymena telomerase, 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 reconstitute Tetrahymena telomerase in 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 with Ronald A. DePinho, produced the first telomerase knockout mouse, [22] showing that although telomerase is dispensable for life, increasingly short telomeres result in various deleterious phenotypes, colloquially referred to as premature aging. [23] In the mid-1990s, Greider was recruited by Michael D. West, founder of biotechnology company Geron (now CEO of AgeX Therapeutics) to join the company's Scientific Advisory Board [24] and remained on the Board until 1997.
Greider accepted a faculty position at the Johns Hopkins University School of Medicine in 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 their telomeres. [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 in Tetrahymena and mammalian systems, Greider also studied telomeres and telomerase in the yeast Saccharomyces 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 2006 Albert Lasker Award for Basic Medical Research for their work on telomeres, [33] before jointly receiving the Nobel Prize in 2009.
In February 2014, Greider was named a Bloomberg Distinguished Professor at Johns Hopkins University. [34]
Greider served as director of and professor at the Department of Molecular Biology and Genetics at Johns 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 Distinguished Professor of Molecular, Cellular, and Developmental Biology at UC Santa Cruz. [36]
Greider's lab employs both student and post-doctoral trainees [37] to further examine the relationships between the biology of telomeres and their connection to disease. [35] Greider's lab uses a variety of tools including yeast, mice, and biochemistry to look at progressive telomere shortening. [38] Greider's lab is also researching how tumor reformation can be controlled by the presence of short telomeres. [38] The lab's future work will focus more on identifying the processing and regulation of telomeres and telomere elongation. [38]
Greider married Nathaniel C. Comfort, a fellow academic, in 1992. They divorced in 2011. She has two children. [39]
A telomere is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.
Tetrahymena is a genus of free-living ciliates, examples of unicellular eukaryotes. The genus Tetrahymena is the most widely studied member of its phylum. It can produce, store and react with different types of hormones. Tetrahymena cells can recognize both related and hostile cells.
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.
The year 1984 in science and technology involved some significant events.
Elizabeth Helen Blackburn is an Australian-American Nobel laureate who is the former president of the Salk Institute for Biological Studies. In 1984, Blackburn co-discovered telomerase, the enzyme that replenishes the telomere, with Carol W. Greider. For this work, she was awarded the 2009 Nobel Prize in Physiology or Medicine, sharing it with Carol W. Greider and Jack W. Szostak, becoming the first Australian woman Nobel laureate.
Thomas Robert Cech is an American chemist who shared the 1989 Nobel Prize in Chemistry with Sidney Altman for their discovery of the catalytic properties of RNA. Cech discovered that RNA could itself cut strands of RNA, suggesting that life might have started as RNA. He found that RNA can not only transmit instructions, but that it can act as a speed up the necessary reactions.
The Hayflick limit, or Hayflick phenomenon, is the number of times a normal somatic, differentiated human cell population will divide before cell division stops.
Michael D. West is an American biogerontologist, and a pioneer in stem cells, cellular aging and telomerase. He is the founder and CEO of AgeX Therapeutics, a startup focused on the field of experimental gerontology.
Joseph Grafton Gall was an American cell biologist whose studies revealed many details of chromosome structure and function. Gall's studies were greatly facilitated by his knowledge of many different organisms because he could select the most favorable organism to study when approaching a specific question about nuclear structure. He was awarded the 2006 Albert Lasker Special Achievement Award. He was also a co-recipient of the 2007 Louisa Gross Horwitz Prize from Columbia University. In 1983 he was honored with the highest recognition of the American Society for Cell Biology, the E. B. Wilson Medal. He had been elected to the American Academy of Arts and Sciences in 1968, the National Academy of Sciences in 1972, and the American Philosophical Society in 1989.
Jack William Szostak is a Canadian American biologist of Polish British descent, Nobel Prize laureate, university professor at the University of Chicago, former professor of genetics at Harvard Medical School, and Alexander Rich Distinguished Investigator at Massachusetts General Hospital, Boston. Szostak has made significant contributions to the field of genetics. His achievement helped scientists to map the location of genes in mammals and to develop techniques for manipulating genes. His research findings in this area are also instrumental to the Human Genome Project. He was awarded the 2009 Nobel Prize for Physiology or Medicine, along with Elizabeth Blackburn and Carol W. Greider, for the discovery of how chromosomes are protected by telomeres.
Telomerase RNA component, also known as TR, TER or TERC, is an ncRNA found in eukaryotes that is a component of telomerase, the enzyme used to extend telomeres. TERC serves as a template for telomere replication by telomerase. Telomerase RNAs differ greatly in sequence and structure between vertebrates, ciliates and yeasts, but they share a 5' pseudoknot structure close to the template sequence. The vertebrate telomerase RNAs have a 3' H/ACA snoRNA-like domain.
Alexey Matveyevich Olovnikov was a Russian biologist. Among other things, in 1971, he was the first to recognize the problem of telomere shortening, to predict the existence of telomerase, and to suggest the telomere hypothesis of aging and the relationship of telomeres to cancer.
Michael Timotee Hemann is an American cancer geneticist and Professor of Biology in the David H. Koch Institute for Integrated Cancer Research at the Massachusetts Institute of Technology. The research in Hemann's laboratory focuses on identification and characterization of genes involved in tumor formation, cancer progression, and chemotherapeutic response.
William Henry Andrews is an American molecular biologist and biogerontologist whose career is centered on searching for a cure for human aging. Andrews is the founder and president of the biotechnology company Sierra Sciences. In the 1990s, he led the team at Geron Corporation that was the first to successfully identify the genes for human enzyme telomerase. This enzyme is responsible for preventing telomeres from shortening in human primordial germ cells.
María Antonia Blasco Marhuenda, known as María Blasco, is a Spanish molecular biologist. She is the current director of the Spanish National Cancer Research Centre.
Bryant Villeponteau is an American scientist, entrepreneur, and longevity expert who has worked in both academia and industry.
Victoria Lundblad is an American geneticist whose work focuses on the genetic control of chromosome behavior in yeast. Many of her discoveries have concerned telomerase, the RNA-containing enzyme that completes the ends of chromosomes. She works at the Salk Institute in La Jolla, California.
Telomeres, the caps on the ends of eukaryotic chromosomes, play critical roles in cellular aging and cancer. An important facet to how telomeres function in these roles is their involvement in cell cycle regulation.
Tetrahymena thermophila is a species of Ciliophora in the family Tetrahymenidae. It is a free living protozoon and occurs in fresh water.
The relationship between telomeres and longevity and changing the length of telomeres is one of the new fields of research on increasing human lifespan and even human immortality. Telomeres are sequences at the ends of chromosomes that shorten with each cell division and determine the lifespan of cells. The telomere was first discovered by biologist Hermann Joseph Muller in the early 20th century. However, experiments by Elizabeth Blackburn, Carol Greider, and Jack Szostak in the 1980s led to the successful discovery of telomerase and a better understanding of telomeres.