October 4, 2007

UCSF's Blackburn Shares Columbia University's 2007 Horwitz Prize

Elizabeth Blackburn

(Adapted from Columbia University news release) Columbia University will award the 2007 Louisa Gross Horwitz Prize to Joseph G. Gall, PhD, a cell biologist at the Carnegie Institution's Department of Embryology, Elizabeth H. Blackburn, PhD, a biologist and physiologist at the University of California, San Francisco and Carol W. Greider, PhD, a molecular biologist and geneticist at the Johns Hopkins University School of Medicine. The awardees, who represent three generations of teacher-student scientists, will be honored for work that has contributed to the fundamental understanding of the aging process. "The relationships among these three researchers represent the best promise of academic medicine - science educators guiding their students toward discovery that furthers understandings for the entire biomedical and science community," said Lee Goldman, MD, executive vice president of Columbia University and dean of the faculties of health sciences and medicine at Columbia University Medical Center. "We are pleased to continue our Horwitz tradition by awarding this year's prize to Joseph Gall, Elizabeth Blackburn and Carol Greider," said David Hirsh, PhD, executive vice president for research at Columbia University. "Our greater knowledge of the aging process, based on their research, is already impacting the study of cell cycles and cell death - which is relevant to understanding neurodegenerative diseases and cancer." The Louisa Gross Horwitz Prize was established by Columbia University to recognize outstanding contributions to basic research in the fields of biology and biochemistry, and has been awarded annually since 1967. The Louisa Gross Horwitz Prize Lectures, presentations by the scientists, will be held on Monday, November 19. Blackburn will give her lecture at 1:30 p.m. in the College of Physicians & Surgeons building, Alumni Auditorium, at Columbia University Medical Center. "These researchers - representing three generations of science passed down from teacher to student - have all contributed to the fundamental understanding of the process of aging, a body of work of enormous depth and value that may lead us to the discovery of keys to longevity and mortality," said Andrew R. Marks, MD, chair of the Horwitz Prize Committee at Columbia University.

Pursuit of Basic Questions about Cell Workings Leads to Insights into Aging and Cancer

Work by these researchers led to discovery of the structure of telomeres and telomerase. It was started to answer two very fundamental questions: what prevents the cell from destroying its own chromosomes, and what prevents the chromosomes from shrinking. Before the late 1970s and 1980s when the prize-winning work was performed, there were two mysteries about chromosomes. One, chromosomes are long lines of DNA so they have two ends, but cells recognize accidental breaks in chromosomes by their broken ends - why don't the cells try to repair the ends of chromosomes? And even if they did, this might have negative consequences, e.g. a cell could join two different chromosomes together. The second puzzle arose following discovery of how DNA copies itself. The process cannot copy the very ends of the chromosomes. So if the DNA is copied repeatedly (as in development, when DNA of one cell is copied in all subsequent cells) the chromosome eventually shortens so much that the cells are no longer viable. Researchers surmised that something unusual was occurring at the ends of the chromosomes, known as telomeres. Using animal models developed by Gall, Blackburn, then a research fellow in his lab at Yale, discovered a special DNA sequence - TTAGGG in humans - that is found nearly identically at the telomeres of nearly every type of animal and plant species. The telomeres protect the ends of the chromosomes and prevent them from opening up, which could result in separation of the two strands of DNA. Thus, the telomeres act as clamps on the ends of the chromosomes. In humans, there are thousands of these segments at the end of a chromosome. Later, in Dr. Blackburn's laboratory at Berkeley, she and Greider, then a research fellow, discovered an enzyme central to aging and cancer, which they named "telomerase." Though Gall, Blackburn and Greider did not set out to answer questions about aging, telomerase has provided answers. The sequencing of the telomeres and the discovery of telomerase has lead to an entirely new field of research that has yielded insights into the mechanisms of aging and the causes of cancer. Because most human cells have limited amounts of telomerase, they have a limited lifespan. Adding telomerase to human cells in culture dishes makes cells immortal, giving telomerase a dark side: almost all cancer cells produce telomerase to fuel their uncontrollable proliferation. Drugs that inhibit telomerase are currently being sought as potential new treatments for cancer.

Pursuit of Basic Questions about Cell Workings Leads to Insights into Aging and Cancer

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