The 2009 Nobel Prizes in chemistry and physiology were awarded this month to a collection of current and former National Institutes of Health grantees.

The 2009 Nobel Prize in chemistry is shared by two grantees of the NIH Thomas A. Steitz, PhD, of Yale University, and Ada E. Yonath, PhD, of the Weizmann Institute of Science, Rehovot, Israel. The two researchers share the award with a former NIH grantee, Venkatraman Ramakrishnan, PhD, of the MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. The three researchers are honored for studies of the structure and function of the ribosome. Ribosomes produce proteins, which in turn control the chemistry in all living organisms.

The 2009 Nobel Prize in physiology or medicine is shared by three current NIH grantees: Elizabeth H. Blackburn, PhD, of University of California, San Francisco; Carol W. Greider, PhD, of Johns Hopkins University School of Medicine; and Jack W. Szostak, PhD, of Massachusetts General Hospital, Harvard Medical School and Howard Hughes Medical Institute. The three researchers, supported by NIH funding for decades, are honored for discovering how telomeres, through the enzyme telomerase, protect chromosomes against degradation. Their discoveries added a new dimension to the scientific community’s understanding of the cell, shed light on disease mechanisms, and introduced new directions for the development of potential new therapies.

The Nobel Prize in Chemistry

Scientists believe an understanding of the ribosome’s innermost workings is important for a scientific understanding of life and that knowledge of a ribosome’s function can be put to a practical and immediate use. Many of today’s antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive, which is why ribosomes have become a prime target for new antibiotics.

The three researchers who share this year’s Nobel Prize in chemistry have generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity’s suffering.“Understanding the ribosome’s inner-workings is important for a scientific understanding of life,” said NIH director Dr Francis S. Collins in a statement. “Thanks to the 3D models created by these three researchers showing how various antibiotics bind to the ribosome, scientists can now develop new antibiotics which will ultimately save lives and decrease suffering.

The NIH began supporting the work of Dr Steitz in 1971, Dr Yonath in 1985, and Dr Ramakrishnan in 1979, and has provided a total of more than $17 million to the three researchers. The NIH’s National Institute of General Medical Sciences (NIGMS) has provided more than $8 million to support the work of Dr Steitz, nearly $4 million to support the work of Dr Yonath, and more than $2 million to support the work of Dr Ramakrishnan.

In addition, the NIH’s National Institute of Allergy and Infectious Diseases and the National Center for Research Resources provided more than $1 million and more than $800,000, respectively, to support the research of Dr Steitz. The National Center for Research Resources also provided more than $800,000 to support the work of Dr Yonath.

The Nobel Prize in Medicine

Cancer and aging research merge in the study of telomeres, the tails at the ends of chromosomes that become shorter as a cell divides. All telomeres have the same short sequence of DNA bases repeated thousands of times. Rather than containing any genetic information, these repetitive snippets help keep chromosomes intact. The enzyme telomerase, which builds telomeres, enables the entire length of the chromosome to be copied without missing the end portion.

The question of how cellular aging relates to abnormal cell division has been the focus of the researchers honored with the Nobel Prize in medicine. During cell division, the ends of the chromosomes are not completely copied, so telomeres become progressively shorter. Over time, scientists theorize, telomeres become so short that their function is disrupted, and this, in turn, leads the cell to stop proliferating. Average telomere length, gives some indication of how many divisions the cell has already undergone and how many remain before it can no longer replicate.

In cancer cells, telomeres act abnormally — they no longer shrink with each cell division. Dr Blackburn and Dr Greider discovered the enzyme telomerase, which is not active in most adult cells, but becomes active in advanced cancers, enabling cells to replace lost telomeric sequences and divide indefinitely. This finding has led to speculation that if a drug could be developed to block telomerase activity, it might aid in cancer treatment. In addition, some inherited diseases are now known to be caused by telomerase defects, including certain forms of congenital aplastic anemia, and some inherited skin and lung diseases.

“The work by Drs Greider, Blackburn and Szostak has been truly groundbreaking and has given researchers worldwide a much better understanding of how telomeres and telomerase affect the life-span of a cell, and in turn, how a cell can become immortal, which is a hallmark of a cancer cell,” said NCI Director Dr John E. Niederhuber.

Dr Blackburn has received NIH funding since 1978, Dr Greider since 1990, and Dr Szostak since 1980. The NIH has provided a total of more than $32 million to the three researchers for their study of telomeres, telomerase, and the molecular functions of cells. The National Institute of General Medical Sciences has provided more than $13 million to support the work of Dr Blackburn, more than $6 million to support the work of Dr Greider, and more than $3 million to support the work of Dr Szostak.

In addition, the NIH’s National Cancer Institute and National Institute of Dental and Craniofacial Research provided more than $2 million and $400,000, respectively, to support the research of Dr Blackburn. Dr Greider has also received more than $7 million in support from the National Institute on Aging. She is also the recipient of a Method to Extend Research In Time Award from NIA and the National Advisory Council on Aging, a grant mechanism initiated by NIH to provide long-term support to outstanding, experienced investigators.

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