Anastasia232: июня 2011

We want to become Nobel laureates

The Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine 2009 awarded to Elizabeth Blackburn, Carol Greider and Jack Shostak "for their discovery of how the enzyme telomerase and telomeres protect the chromosome. Mechanism to protect chromosomes from shortening with each division was first predicted in 1971 by Alexey Matveyevich Olovnikov and subsequently its theoretical constructs have been confirmed in practice, experimenters, and are worthy of the Nobel Prize. Telomeres play a role in age-related changes of cells and the whole body and in the development of malignant diseases. Further investigation of the dynamics and principles of the extension is to the enzyme telomerase can help find new ways to fight aging and cancer.

Elizabeth Blackburn was born in 1948 in Australia - in Hobart, the capital of Tasmania - a family of doctors. When she was a schoolgirl, her family moved to Melbourne, where Blackburn was studying at Melbourne University in college and in the magistracy. Then she enrolled in graduate studies at Cambridge and received his Ph.D. there. Subsequently, Blackburn worked for two years at Yale, and then (in 1978) moved to the University of California at Berkeley, where he made her most important discoveries related to telomerase. In 1990, she moved to another branch of that great university - University of California, San Francisco, where he works to this day. In addition, she is an employee of the Salk Institute (Salk Institute) in San Diego, and from 2002 to 2004 she worked in the President's Council on Bioethics. Its exclusion from the council associated with her position on embryonic stem cell research, which was displeasing to the administration of George W. Bush vetoed federal funding for these critical studies. In April this year, Blackburn was elected president of the American Association for Cancer Research (American Association for Cancer Research) and next year should lead this association.
Carol Greider was born in 1961 in San Diego (California). In 1983 she received a bachelor's degree from the University of California at Santa Barbara, then moved to the University of California at Berkeley, where her supervisor was Elizabeth Blackburn. Already in 1985 in the journal Cell, published an article Greider and Blackburn, announces the opening of telomerase. After receiving his doctorate in 1987, Greider became an employee of the Laboratory in Cold Spring Harbor (Cold Spring Harbor Laboratory), and in 1997 he moved to Johns Hopkins University, where he still works as a professor. Laboratory, headed by Carol Greider, a continuation of telomeres and telomerase.
Jack Shostak was born in London in 1952. Soon after his parents moved to Montreal, where he was in college at McGill University and in 1972 became a bachelor. He received his doctorate in 1977 at Cornell, where he remained for two more years, then moved to Harvard Medical School, where he works today, professor of genetics. In addition to Harvard, Shostak is a member of two other institutions - the Massachusetts General Hospital (Massachussets General Hospital) and the Howard Hughes Medical Institute (Howard Hughes Medical Institute). In addition to the opening of telomerase, Shostak first synthesized yeast artificial chromosomes. Creating these artificial chromosomes is widely used in mapping the genes of animals, including humans, and in the development of genetic engineering technology. Currently, the Harvard lab Shostak deals primarily with issues related to the origin of life, and works on the artificial synthesis of living cells.

Telomeres - the terminal regions of chromosomes, consisting of repeated sequences of nucleotides - were discovered in the fifties of the XX century. Telomeres can be seen even in the light microscope: preparing to divide or dividing cells can be painted so that the telomeres of a different color from the central parts of each chromosome. Telomeres are present only in eukaryotes (organisms whose cells have a kernel), and in bacteria and archaea are closed in a ring chromosome, and telomeres do not have. These end parts of chromosomes do not contain genes: recorded at telomeres information is not read at mRNA and did not encode. Actually, the information in the telomeres contained very little, because they consist of repeating the same sequence of several nucleotides. These sequences are fairly uniform. In particular, in all vertebrates, as well as many fungi and protists is always TSTSTSTAA, and higher plants - seems to always TSTSTSTAAA.

Alex Matveyevich Olovnikov, Institute of Biochemical Physics, in 1971 formulated the theoretical concept, presupposes the existence of an enzyme that is open in the early eighties, Carol Greider and Elizabeth Blackburn and they called telomerase. Studies of this enzyme, carried out in laboratories Blackburn and Shostak, confirmed the validity of some theoretical conclusions Olovnikov. Photo from moikompas.ru

Initially, the function of telomeres were unknown, as was not known and the sequence of their component nucleotides. In the late fifties, was discovered enzyme, DNA polymerase, providing a doubling of the DNA molecules. To get started, this enzyme must adhere to another enzyme synthesized primers - short sitting on the DNA fragment of RNA, which was subsequently removed. In this case, DNA polymerase can move along the DNA chain in only one direction - from the 5'-end to 3'-end. As a result of DNA polymerase can not completely copy the entire DNA molecule: on one end, to which it is attached, should remain uncopied fragment. At first it drew attention, independently of each other, Alexei Matveyevich Olovnikov (Olovnikov AM 1971. Marginotomii principle in the matrix synthesis of polynucleotides, Dokl Akad. T. 201. S. 1496-1499; Olovnikov AM 1973. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon / / Journal of Theoretical Biology. V. 41. P. 181-190) and James Watson (Watson JD 1972. Origin of concatemeric T7 DNA / / Nature New Biology. V. 239. P. 197-201). It turned out that the chromosomes should be shortened with each cell division due to uncopyable whereas end sections. Watson has suggested how this problem should be solved with bacteriophage, DNA, which is also not closed in a ring, and Olovnikov described how it can be solved in eukaryotes, and conjectured about the existence of an enzyme capable of adding to the end of the chromosome repetitive sequences. He also suggested that the regulation of this enzyme may play a key role in the aging organism (due to the gradual shortening of end sections of chromosomes in cells that have divided only a limited number of times) and that defects in the mechanism of such regulation can cause uncontrolled cell division in malignant tumors .

Soon, the telomeres of some organisms were really open repetitive sequences. Experiments were conducted in the laboratory of Jack Shostak, Harvard Medical School, showed that foreign DNA fragments that are embedded in yeast cells, are capable of doubling, but, unlike the yeast's own DNA, there are dividing cells for long. Elizabeth Blackburn, as a graduate student at Cambridge, has mastered developed at that time, techniques of DNA sequencing (reading the sequence of nucleotides) and later at Yale has found exactly what the sequence is repeated at the ends of chromosomes in the ciliate Tetrahymena thermophila (TSTSTSTSAA). Met at a conference in 1980, Shostak and Blackburn have conceived a joint experiment, whose results indicated that it telomeres protect their own yeast chromosomes from degradation due to repeated cell division. Researchers have connected the fragments with a repeating sequence of nucleotides found in ciliates, a small alien DNA fragments derived and implemented a molecule in yeast cells. Such molecules are successfully doubled in yeast cells, along with its own chromosomes, yeast, and at their ends to end up repeating the sequence of nucleotides, typical of its own yeast telomeres. The publication of these results in the journal Cell was the first work we have experimentally demonstrated the protective role of telomeres.

Terminal region of the chromosome - telomeres (telomere). Each chromosome (chromosome), contained in the core (nucleus) cells (cell), before cell division is represented by two identical halves - chromatids, based on each of which is a very long, but compactly coiled DNA molecule at each end of which there are areas of repetitive sequences. These end parts and have telomeres. In preparation for the division when chromatids are doubled, the ends of each chromosome always be shortened (the mechanism of DNA doubling does not allow to copy them), if the enzyme telomerase does not increase at the ends of new repetitive sequences. Illustration from the site of the journal Nature (www.nature.com)

Shostak, and Blackburn, after Olovnikov suggested that increasing telomere ensured by a certain enzyme. Began the search for this enzyme. In 1984 he was first able to distinguish Carol Greider, who was then still a student and worked under the guidance of Elizabeth Blackburn. In the paper, published in Cell, Greider and Blackburn for the first time describe the properties of their discovery of the enzyme telomerase, and called him. By studying this enzyme, they found its constituent RNA fragment, the matrix is synthesized and repetitive nucleotide sequences that are added to the telomerase terminal regions of chromosomes. This discovery was described in a paper published in Nature.

Scheme of the telomerase enzyme (telomerase). Enzyme increases the terminal chromosome regions, adding to them the same nucleotide sequence. This process involves two successive stages: (a) elongation, that is, elongation, and (b) translocation, ie movement. During the elongation of the terminal portion of the DNA chain is associated with the RNA matrix (RNA template), which is part of the enzyme, and lengthened by acceding to the nucleotide complementary to free areas of the matrix. During translocation, the DNA molecule is shifted by a few nucleotides, re-releasing the RNA portion of the matrix, and the cycle repeats. At the same time built up only one DNA chain, but a complex of other enzymes, which is based on the DNA polymerase completes most of the second chain. Remains only a small single-stranded "tail" at the very end. If it were not for telomerase, such tails cut to a length of double-stranded DNA each time it doubles, and each chromosome would be shortened with each cell division. Drawing from the site barleyworld.org

Further studies conducted in laboratories Blackburn and Shostak, showed that cells lacking telomerase eventually stop dividing and die. Many types of cancer cells, in contrast, have increased activity of telomerase, which contributes to their uncontrolled division and the formation of malignant tumors. As suggested Olovnikov, telomeres have been an important tool for the regulation of both aging and cancer. There are already developed and tested drugs, which may allow to deal with a number of forms of cancer by suppressing the activity of telomerase in cancer cells.

Since the work of telomerase is also related to the development of congenital dyskeratosis (dyskeratosis congenita) - a rare hereditary disease that causes premature aging. Symptoms of the disease are associated with impaired regulation of telomere length. Congenital dyskeratosis yet know how to treat, but further studies may allow to find ways to stop its development.

Although the general principle of telomerase is unclear, yet to find out many important details, in particular the regulatory mechanisms that prevent telomeres indefinitely to grow and define their decline in aging cells. As regards the role of telomeres in aging, there also remains much remains unclear, although the reduction of their length really is typical for the aging of eukaryotic cells.

According to the will of Alfred Nobel, each award may share no more than three scientists. It is a pity that among the winners of this award is not entered Olovnikov, who predicted a marked its opening. However, Blackburn, Greider and Shostak, who devoted many years of successful experimental studies of telomeres and telomerase, certainly deserving of this award.

This year, a Nobel prize for the first time in the history shared by two women. Among those who examine the telomere today, women, unusually many. Perhaps it is no coincidence: the example of Elizabeth Blackburn and Carol Greider, discovered telomerase and to determine the structure of this enzyme, inspires other women to continue research in this area.

The Nobel Prize in medicine went to scientists who were able to describe the method by which you can copy the entire chromosome during cell division, and thus prevent their degradation. The names of the heroes of yesterday - Elizabeth Blackburn, Carol Greider and Jack Shostak. For his contribution to science, they will receive 10 million Swedish kronor (about one million euros). "The merit of scientists received the Nobel Prize, is to open a fundamental mechanism in the cell, the use of which leads to the development of new therapeutic strategies. Advances Blackburn, Greider and Shostak added a new dimension to our understanding of cells, shed light on the mechanisms of disease and stimulated the development of new therapies, "- these words described the achievement of medical Nobel Committee awarded prizes.
The work done by a group of scientists, will, among other things, used and in finding mechanisms to combat aging. According to Nobel Prize winners, special care should be considered end parts of chromosomes, telomeres, and an enzyme called telomerase, from which they are composed. Telomeres, in turn, are the "alpha and omega" of the chain

Anastasia232

вторник, 7 июня 2011 г.

We want to become Nobel laureates

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Архив блога

вторник, 7 июня 2011 г.

We want to become Nobel laureates

Постоянные читатели

Архив блога

вторник, 7 июня 2011 г.