Article published in September 2012.

 

Agustín Vioque
Instituto de Bioquímica Vegetal y Fotosíntesis, Universidad de Sevilla y CSIC
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One of the most relevant researchers in the field of RNA, Joan Steitz did pioneering work in the study of translation initiation, determining the sequences involved in translation initiation in a messenger RNA (mRNA), and showing that there is base pairing between 16S ribosomal RNA and mRNA at initiation. But mainly she is known for the discovery of small nuclear ribonucleoproteins (snRNPs) and their role in splicing.

 

Joan was born in Minneapolis. She studied chemistry at Antioch College (Ohio). Despite her interest in research, she decided to study medicine because she knew some women doctors but she did not know any women scientist or women science professors at major universities. However, the summer before going to Medical School at Harvard she returned to Minneapolis and found a summer job in Joe Gall's lab at the University of Minnesota. Gall recognized her talent and persuaded her to enter a doctoral program instead of studying medicine. She was admitted to the PhD program in Molecular Biology at Harvard University, where Joan was the only woman, and did her doctoral thesis under the supervision of James Watson.
After obtaining the PhD she moved to Cambridge, where she made her first major independent contribution, identifying the start sites of translation in the mRNA of a bacteriophage. Years later she showed that the ribosome binds to the site of initiation of translation by forming a helix between the 16S rRNA and the mRNA.
In 1970 Yale University offered her a job and at present she continues in the same University as Sterling Professor (the highest distinction at this university) of Molecular Biophysics and Biochemistry.
In 1979 her laboratory made the crucial discovery that the blood of patients with lupus, an autoimmune disease, contains antibodies that react with small nuclear ribonucleoproteins (snRNPs). These antibodies gave her tools necessary to demonstrate that snRNPs called U1, U2, U4, U5 and U6 are involved in the splicing mechanism. Her laboratory has been a reference in the elucidation of the mechanism for removal of introns and, for example, showed that snRNP U1 recognizes the 5 ' side of introns by forming a helix between the U1 RNA and the pre-mRNA. Other relevant contributions have been the discovery of snRNPs U11 and U12, which are part of an alternative mechanism involved in removing a minor subset of introns, and snoRNAs, involved in the modification of ribosomal RNA.
Joan Steitz is a member of the National Academy of Sciences of the United States, among other institutions, and has received numerous honorary doctorates and awards, including the National Cancer Institute's Rosalind E. Franklin Award for Women in Science, the Gairdner Foundation International Award and the Albany Medical Center Prize in Medicine and Biomedical Research in 2008, the best endowed prize in Medicine after the Nobel Prize.
Her laboratory continues to be highly productive in the field of RNA, consistently generating high impact publications.
 

joansteitz

 Joan Argentsinger Steitz

 

REFERENCES

 

1. Steitz JA (1969) Polypeptide chain initiation: nucleotide sequences of the three ribosomal binding sites in bacteriophage R17 RNA. Nature 224, 957-964.
2. Steitz JA, Jakes K (1975) How ribosomes select initiator regions in mRNA: base pair formation between the 3' terminus of 16S rRNA and the mRNA during initiation of protein synthesis in Escherichia coli. Proc. Natl. Acad. Sci. USA 72, 4734-4738.
3. Lerner MR, Boyle JA, Mount SM, Wolin SL, Steitz JA (1980) Are snRNPs involved in splicing? Nature 283, 220-224.
4. Woodbury M (2006) Trailblazer turned superstar. HHMI Bulletin 19, 21-23.
5. Yale Bulletin & Calendar 16 de mayo 2008, 36(29) (http://www.yale.edu/opa/arc-ybc/v36.n29/story7.html)
6. Profile: Joan Argentsinger Steitz. ASCB Newsletter, June 2006, 18-20.

Article published in September 2012.

 

Nuria Martínez Medina
Sección "Historia de la Ciencia" del programa "A hombros de gigantes" de Radio 5, RNE
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In 2009, Carol Greider shared the Nobel Prize in Medicine with Elizabeth Blackburn and Jack Szostak for the discovery of telomerase, an enzyme responsible for maintaining telomeres. These are regions of DNA found at the end of chromosomes (from the Greek telos, end, and meros, part). As a normal cell divides the telomeres disappear, causing a progressive functional decline and, ultimately, death. This process explains why normal cells can die. However, tumor cells can maintain their telomere size thanks to the extra production of telomerase. 30 years ago this process was unknown, and only a few scientists worked in this field. Those few included Elizabeth Blackburn and her pupil, Carol Greider.

 

Carolyn Widney Greider was born in San Diego, California, on April 15th, 1961. Daughter of a physicist and a PhD in Botany, she is the youngest of two kids. Her childhood was deeply marked by her mother´s death, when she was six. She finished high school with bad marks due to the dyslexia she was suffering, but she was accepted by the University of California at Santa Barbara, where she graduated in Biology in 1983. In March 1984, she began her doctoral studies at UC Berkeley, where she met Elizabeth Blackburn, who was investigating at the time the elongation of telomeres. "I was intrigued by this matter, Carol recalls in an autobiography, so I applied for working in Elisabeth's laboratory."
Blackburn remembers her student as a person of great rigor and entrepreneurship, two basic qualities to become a leading researcher and not letting herself being "intimidated" by the project undertaken (4). In addition, Carol completed her knowledge of Biochemistry with DNA cloning techniques and other skills which were necessary for her work (2).
Christmas Day, in 1984, was the key date. At only 23 years old, while other kids were having fun, Greider identified in the laboratory the enzyme telomerase, responsible for protecting the integrity of chromosomes (1). This discovery helped launching a research field which attracted the attention of longevity researchers, cancer biologists, and the biotechnological industry (3).
In 1993 she married the science writer Nathaniel Comfort, with whom she has two children. Since 1997, she works in the Department of Molecular Biology and Genetics at Johns Hopkins University, where she is Professor and Director of the Department. "Having two kids and a full time job in the lab is a challenge, but having Charles and Gwendolyn is the best thing that has ever happened to me. My lab knows that I am a mom first, and the flexibility that academic science provides makes having a career and a family possible. I can go home when needed, or to a school play in the middle of the day, then come back and finish my work-day; or work from home on the computer. The main thing is to find the time to get things done, it is not the hours at work but the overall productivity that counts. Having flexibility takes a huge amount of pressure off" (5).
When in 2009 she was awarded with the Nobel Prize, her first reaction was of disbelief, turning later into satisfaction and pride. "One of the lessons I have learned in the different stages of my career is that science is not done alone. It is through talking with others and sharing that progress is made. (...) The new ideas quickly become part of the collective consciousness. This is how science moves forward and we generate new knowledge".

 

carolgreider

 Carol Greider

 

REFERENCES

 

1. Greider CW and Blackburn EH (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43: 405-413.
2. Greider CW and Blackburn EH (1989). A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337: 331-337.
3. Greider CW (1991). Telomerase is processive. Mol. Cell Biol. 11: 4572-4580.
4. Biography of Carol W. Greider.
http://www.pnas.org/content/102/23/8077.full
5. Autobiography. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/greider.html
 

 

Article published in August 2012.

 

Álvaro Martínez del Pozo
Dpto. de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid
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Jane S. Richardson represents a paradigmatic example of how unique can be a scientific carrier. She graduated in philosophy, accompanied her husband as a technician, and never got a Ph. D. degree. However, she has made seminal contributions to the field of protein structure and has accomplished the highest scientific ranks, such as the membership of the U.S.A. National Academy of Sciences and the presidency of the Biophysical Society. The way we understand and represent protein structures today was essentially developed by her. 

 

Jane showed her scientific ability at a very early age. Still a teenager, she ranked third at the prestigious Westinghouse Science Talent Search, a national contest where she calculated the orbit of Sputnik from observations on two successive nights. This interest in astronomy led her to Swarthmore College, although she finally ended up graduating in philosophy, with a minor in physics, in 1962. That same year she married David C. Richardson, who decided to pursue a doctorate in chemistry at the Massachusetts Institute of Technology (MIT). Jane followed him, and obtained master's degrees in both philosophy and teaching from Harvard University in 1966.
Jane did not feel herself suited for teaching and then decided to join her husband laboratory at MIT as a crystallographic technician, starting a long-lived collaboration which still endures. After 7 years of work, in 1969 they published the 10th protein structure, corresponding to the Staphylococcal nuclease.
In 1970 David was offered a Faculty position at Duke University which held a policy against hiring married couples in the same department. Jane managed to hold several different positions continuing with their collaboration. In many regards, she was indeed the scientist leading the team. By 1974 they had solved the high resolution structure of another protein, a bovine superoxide dismutase. According to her ever increasing role within their scientific couple, by 1977 Jane published a milestone article where she reviewed the β-sheet topology and led to the definition of the Greek key β-barrel fold. Jane also created the ribbon drawings we all still use today to represent protein structures. In 1990, altogether with David, they pioneered molecular graphics for personal computers and developed methods to measure goodness of fit inside proteins and its interactions with molecules.
Jane and David have continued making breakthrough contributions that cannot be treated in this article. They have pursued the development of new methods and software to quantify and visualize molecular interactions and design new therapeutic drugs. Lately, they have expanded their macromolecules landscape by successfully incorporating RNA within their repertoire.
Maybe the best definition of Jane was given by S.H. White in 1992: "Jane is a philosopher, a scientist, and (although she claims otherwise) an artist. Who can forget her now famous 1977 paper in Nature in which β-sheet structural motifs were described in terms of patterns painted on Grecian urns? She could see a motif common to complex protein structures and to the Greek key design. In seeing such connections, she helps us to recognize the great beauty inherent in science and establishes a common ground between science and human aesthetics". Jane never got a doctoral degree but she holds three honorary doctorates and has risen to the Olympus of protein chemistry and structure.
  

janerichardson

 Jane S. Richardson

 

REFERENCES

1. N. Kresge et al. (2011) J. Biol. Chem. 286:e3.
2. J.S. Richardson (1977) Nature 268:495.
3. (http://en.wikipedia.org/wiki/Jane_S._Richardson).
4. (http://www.chemheritage.org/discover/chemistry-in-history/themes/biomolecules/proteins-and-sugars/richardson.aspx).
5. Richardson Laboratory at Duke University (http://kinemage.biochem.duke.edu/lab/Richardson/richardson.php).
6. S.H. White (1992) Biophys. J. 63:1185.

 

 

Article published in August 2012.

 

Roser González-Duarte
Dpto. de Genética, Facultad de Biología, Universidad de Barcelona
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Elizabeth H. Blackburn, Nobel Prize in Physiology or Medicine in 2009 with Carol W. Greider and Jack W. Szostak, is a scientific reference in modern Molecular Biology because she led to the discovery of telomerase and its role in the elongation of the ends of eukaryotic chromosomes after each round of replication, contributing to the stability of telomeres. She currently works hard to identify additional functions of telomerase and to elucidate its relation to cell aging and cancer. Her scientific contributions stand out for their quality and experimental rigor. The perusal of her biography brings out especially her intellectual and human qualities, including perseverance, discretion and a high sense of responsibility. 

 

Elizabeth Helen Blackburn was born in 1948 in Tasmania (Australia). From an early age she was attracted by the lush, rich animal diversity of the natural environment in southern Tasmania, and learned to watch it carefully. She finished high school with honors and won a scholarship to graduate in Biochemistry at the University of Melbourne. Elizabeth´s first big professional break was in 1970, as she was admitted as a pre-doctoral student in the famous laboratory of the Medical Research Council (MRC) in Cambridge (United Kingdom), where Watson and Crick had elucidated the structure of DNA. In addition, her thesis director would be Fred Sanger, a scientific reference and Nobel Prize in Chemistry for elucidating the structure of insulin (1958). As a research topic, Sanger suggested her to sequence RNA fragments. While working on this, Elizabeth met an American postdoc who later became her husband, John Sedat, who would reaffirm her interest and willingness to learn from science and research with great methodological rigor. With these premises, in 1975 she began a postdoctoral stay in Joe Gall's lab at Yale University (USA). Gall had begun the cultivation of Tetrahymena, a ciliated protozoan whose genome is composed of many small linear minichromosomes, and had developed a method to purify them. The proportion of chromosomal ends relative to the rest of the chromosomal DNA was far superior to that of eukaryotes studied so far. Tetrahymena was therefore a good model to identify these terminal chromosomal sequences, called telomeres. Blackburn showed that Tetrahymena´s telomeres consisted of short repeated sequences in tandem, rich in guanine (G) and thymine (T), whose synthesis depends on a new enzymatic activity. These results, really surprising, were published in Nature in 1984. Blackburn established as a priority to identify the protein responsible for copying the repeated sequences that she had described. In this phase of work, the contribution of Carol Greider, from the California Institute of Technology (Caltech), is absolutely essential. Carol, used to fight hard against severe dyslexia, enriched the team with her great perseverance and her extreme experimental rigor. These are key qualities who would help to finally describe the contribution of telomerase in the elongation of DNA chains and unveil the mechanism that compensates the incomplete replication of the ends of linear chromosomes. Later, they demonstrated that telomerase is a ribonucleoprotein present in various eukaryotic species with reverse transcriptase activity, which also contains the RNA used as a template to extend the 3' chains protruding chromosomic ends. Subsequent studies have shown that telomerase is associated with aging and is associated with many tumor pathologies. For this reason, the telomeres remain at the forefront of scientific landscape, and Blackburn, along with other researchers, is working to elucidate new functions of telomerase and help the design of anti-cancer therapies.

  

elizabeth_blackburn

 Elizabeth H. Blackburn

 

REFERENCES

1. Brady C. (2007). Elizabeth Blackburn and the Story of Telomeres. The MIT Press.
2. Blackburn EH. (2009) Nobel Lecture
http://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/blackburn-lecture.html
3. Blasco MA, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91(1):25-34.

 

 

Article published in July 2012.

 

Adela Muñoz Páez
Dpto. de Química Inorgánica, Facultad de Química de la Universidad de Sevilla
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60 million people affected, more than 22 million dead people, a continent -Africa- on the verge of collapse. Although AIDS has been the most frightening epidemic of the XXth century, the disease is no longer an imminent death sentence thanks to the work of scientist. Especially that of Professor Françoise Barré-Sinoussi, Medicine Nobel Prize laureate together with Professor Luc Montaigner in 2008 (1), for the identification and isolation of the human immunodeficiency virus, HIV, causing the illness. 

 

Born in Paris in 1947, she became interested in nature during her holydays in Auvergne while at school she obtained the best marks in sciences. She took an undergraduate degree in Sciences at the University of Paris because it was shorter and less expensive than a degree in Medicine, her initial choice. She started doing unpaid work at the laboratory of Professor Jean-Claude Chermann, at the Institut Pasteur at Paris, who finally supervised her thesis devoted to the study of the relationship between retroviruses and cancers. After finishing it in 1974, she spent a sabbatical year at the National Institute of Health in Bethesda, USA, and then came back to the Institut Pasteur. When at the end of 1982 some patients were diagnosed with a contagious strange illness which what not affected by antibiotics or any other known treatment, she was in charge of the research to find out if the infectious agent was a virus.
It is difficult to realize now how formidable this task was. In fact the appearance of such an illness was a shock in the first world. Nothing similar has been found before, because it destroyed the immunologic system that is why it was called Acquired Immunodeficiency syndrome, AIDS. For this reason the body was attacked and killed by pathogens that in normal conditions would be harmless. It was called the "pink plague", because it attacked mainly homosexuals. Panic spread as well as homophobic and puritan feelings. Hollywood actors headed a movement to remove the stigma of the illness, but the works carried out by scientist proved to be more efficient. AA few months after having started her research, in May 1983, Françoise and her coworkers published the first work (2) identifying the agent responsible for the illness, later to be called VIH. It was one of the quickest answers in the history of medicine to identify the origin and provide treatment for a new disease. After the discovery of Prof. Barré-Sinoussi, major advances in laboratories all around the world brought drugs development and as a result the once lethal illness was transformed into a chronic one. Moreover, the faith in the power of science was recovered by mankind.
Although the success was great she did not stopped working because the VIH virus had not been fully defeated. On one hand as head of the Retrovirus unit from the Pasteur Institute in Paris, (3) she keeps investigating to obtain a full recovery of the AIDS patients and an efficient vaccine to prevent it. On the other hand, as a person with a commitment to help people sick with AIDS, she pays regular visits to the sub-Saharan African countries, where most part of the 33 millions of affected people live, to devise strategies to fight the illness. She even answered the Pope when at the beginning of a visit to Africa in 2009 he dismissed the importance of using condoms to prevent AIDS recommending abstinence instead, by addressing him a strong open letter published in Le Monde (4).
Bright scientist, endless worker, fighter to improve the health of the poorest, without fear to criticize the highest authorities... On top of all that Françoise Barré-Sinoussi has a witty sense of humor (5) which renders her irresistible. 
  

barré-sinoussi

 Françoise Barré-Sinoussi

 

REFERENCES

1. Françoise Barré-Sinoussi (2008) Autobiography. Nobelprize.org:http://www.nobelprize.org/nobel_prizes/medicine/laureates/2008/barre-sinoussi.html
2. Barré-Sinoussi F y col. (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science, 4599: 868-871
3.http://www.pasteur.fr/ip/easysite/pasteur/en/research/scientific-departments/virology/regulation-of-retroviral-infections/regulation-of-retroviral-infections
4.http://www.lemonde.fr/idees/article/2009/03/24/lettre-ouverte-a-benoit-xvi_1171956_3232.html
5.http://www.youtube.com/watch?v=Kz-_-daSSl4

 

 

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