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Mass. General researcher Szostak shares
Lasker Award for Basic Science
Scientists honored for discoveries
related to telomerase, enzyme that protects chromosome tips
BOSTON - September 17, 2006 - Jack W. Szostak, Ph.D., of
the Massachusetts General Hospital Department of Molecular Biology
and Harvard Medical School is a co-recipient of the 2006
Lasker Award for Basic Medical Research, which was announced
on Sunday, Sept. 17. Presented by the Albert and Mary Lasker Foundation,
the Lasker Awards are often considered the American version of the
Nobel Prize, and many Lasker recipients have gone on to win the
Nobel.
Szostak is a co-recipient of the basic research award with Elizabeth
H. Blackburn, PhD, of the University of California at San Francisco
and Carol W. Greider, PhD, of the Johns Hopkins School of Medicine.
They are being honored for their work predicting and then discovering
telomerase, an enzyme that builds and maintains the protective caps
at the tips of chromosomes. These structures, called telomeres,
play essential roles in maintaining proper chromosome structure
and behavior.
The existence of telomeres was hypothesized in the 1930s from the
observation that broken chromosome fragments fuse with each other
and lead to chromosomal abnormalities, something that normal chromosome
ends never do. Blackburn had been studying the telomeres of a single
cell protozoan, Tetrahymena, and had found that they were
composed of a repeated sequence of six nucleotides. She and Szostak,
a yeast geneticist, met at a research conference in 1980 and decided
to collaborate to see whether the repeated sequence she had discovered
would work as a telomere in yeast.
The experiment showed that the repeated protozoan sequences did
act as telomeres, protecting yeast DNA segments from degradation
and integration into the yeast genome. Further work by Szostak and
Blackburn led to the discovery that normal yeast chromosomes had
a related but distinct structure. Their most surprising observation
was that Tetrahymena telomeres, when placed in yeast, grew
in length by the addition of new yeast-type sequences to the end
of the DNA. This work led to the prediction of a new enzyme that
was adding the protective sequences to the chromosome tips.
Blackburn and Greider went on to detect and isolate this enzyme,
now known as telomerase, and to describe the enzyme's structure.
During the same period Szostak and his postdoctoral fellow Victoria
Lundblad, now at the Salk Institute, used genetics to identify a
protein essential for maintaining telomeres in yeast, which turned
out to be a key component of telomerase. Their work showed for the
first time that the inability to add telomere repeats to the ends
of chromosomes led to telomere shortening and eventually, after
many cell divisions, to cell death. This was the first link between
the molecular biology of telomeres and cellular senescence, the
aging and death of cells.
Although the work of the Lasker awardees was not known to be relevant
to human disease when it was carried out in the 1980s, subsequent
studies of telomeres and telomerase in human cells have shown that
the enzyme plays crucial roles in both cancer and aging. As a result,
telomerase is being intensely studied by many research groups, including
Blackburn's and Greider's teams.
Szostak's research group has followed a different path in recent
years and has been investigating
the molecular origins of life. They are seeking to understand
how complex chemicals were able to self-assemble and combine to
form simple organisms that can reproduce and evolve. Currently they
are working to develop simple cell-like structures incorporating
both a nucleic acid - such as RNA or DNA - to transmit genetic information
and an enclosing membrane. Other scientists within Szostak's lab
are investigating ways to use the cell's protein-making machinery
to create molecules of interest, such as new antibiotics, and using
the power of natural selection to create and study new RNA and protein
sequences.
Szostak is the Alex Rich Distinguished Investigator in the Department
of Molecular Biology at Massachusetts General Hospital, a Professor
of Genetics at Harvard Medical School and a Howard
Hughes Medical Institute Investigator. He is a graduate of McGill
University and holds a Ph.D. from Cornell University.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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