Monday, October 5, 2009

"Abhi to main jawan hoon..." + "how chromosomes are protected by telomeres and the enzyme telomerase"

When Elizabeth Blackburn last visited India on a lecture tour, introductory note inviting for her lecture read: "Nehru Memorial Museum and Library: Award-winning biologist and professor at University of California Elizabeth Blackburn will speak on “Chromosome Ends and Human Health and Disease”, Teen Murti Auditorium, Teen Murti House, 4:30 p.m."After following this and her non-stop talk lasting above an hour, it was clear how she was successfull in radiating her energy in jargon-less presentation along with consistent enthusiasm to appeal girls and young minds to take a giant leap to study this area which ultimately marched towards Nobel of 2009.


Significance of the discovery made by Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak can be guaged from the starting words of the press release: "This year's Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase." (http://nobelprize.org/nobel_prizes/medicine/laureates/2009/press.html


This is the first time that two women are sharing the Nobel prize in entire history of Nobel prizes. The discovery is key in finding many answers of ageing and decay of immune system in cancer. As release further elaborates, "If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies."


This award also reflects inspiring story of student and teacher sharing the hallmark of greatest glory in scientific acheivement. Carol Greider who is Proffessor of Molecular Biology in Johns Hopkins University and Genetics will be sharing prize with Szostak was graduate student of third co-winner Blackburn and she completed Ph.D. from California University, Berkeley.


The efforts directed at approaching path breaking solutions to cancers can be understood from her words: "
To understand how telomere functions to provide chromosome stability and how telomerase might play a role in cancer, we generated a telomerase null mouse. Mice that lack the gene encoding the mouse Telomerase RNA (mTR) show progressive telomere shorting during successive breeding. The mice are viable for up to six generations although in the later generations there is severe reduction in fertility due to apoptosis in the germ cells. Crosses of these telomerase null mice to other tumor prone mouse models suggest that under some circumstances tumor formation can be greatly reduced when telomerase is absent. This suggests that telomerase inhibition may be a useful approach to cancer treatment." (http://www.hopkinsmedicine.org/pharmacology/research/greider.html)


Third legend in the group is Jack W. Sztostak in Department of Genetics & Molecular Biology at Cambridge St. A Ph.D. from Cornell University, this man is member of all premier acadamies like National Academy of Sceinces, American Academy of Arts and Sciences and New York Academy of Sciences.

"At the outset of his career, Szostak made pioneering contributions to the field of genetics. His discoveries helped clarify the events that lead to chromosomal recombination—the reshuffling of genes that occurs during meiosis—and the function of telomeres, the specialized DNA sequences at the tips of chromosomes. He is also credited with the construction of the world's first yeast artificial chromosome. That feat helped scientists to map the location of genes in mammals and to develop techniques for manipulating genes. " (http://www.hhmi.org/research/investigators/szostak_bio.html)

But a Nobel Prize–winning discovery in the 1980s by former HHMI President Tom Cech and Sidney Altman transformed Szostak`s research. This discovery demonstrated that RNA, the sister molecule of DNA, can catalyze certain chemical reactions inside cells, a job previously thought to be the exclusive domain of proteins. This new revelation about RNA's dual role suggested to some scientists, including Szostak, that RNA likely existed long before DNA or proteins because it might be able to catalyze its own reproduction. Their discovery made it easier to think about the origin of life. (life.http://www.hhmi.org/research/investigators/szostak.html)


Blackburn who is distnguished recipient of six honorary doctorates from renowned universities, not to mention the legendary awards and membership from across the world. Most importantly her research vindicates other scientist`s work focussing on potential of diet, exercise, stress reduction and other "lifestyle interventions" in reducing the risk of and reverse damage from coronary artery disease and stave off diabetes. She was consistently emphasising on this mind-body link now being fertile territory for prominent research scientists when she referred to her experience during the talk she delievered few months ago in India.
(Her major list of publications is available at http://cancer.ucsf.edu/people/blackburn_elizabeth.php.)


Fountain of Youth:
In a recent interview she says, "For now, the best defense is healthy living, she said. The goal should not be to live to 150 years old but to live well for 80 or 90 years. In an ideal world, people would protect their telomeres during the years they're normally susceptible to diseases of aging. Then they would "fall off the perch" and die, as genetically programmed, at 90 or even 100 years old. Scientists used to believe that everyone's telomere length shortened over time, the same way they used to think that brain neurons stopped growing in the elderly. But telomere length, while it does decline in general, fluctuates in individuals. Many older people have relatively long telomeres. Eventually she indicates towards a way where drugs will play a lesser role and study of our body's physiology should play a major role in enabling us to arrive at a age when we will sing "Abhi to main jawan hoon..." "(http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2009/01/02/CMBO14L1P9.DTL&type=health)


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