The tale of telomerase

Carol Greider delivered a fascinating plenary lecture last night - the tale of telomerase is so thought-provoking! 

Telomeres are the protective ends of a chromosome - I've heard them described as a bit like the plastic piece on the end of a shoelace, which protects the lace from fraying each time it's tied. Unfortunately, every time a cell divides, it loses a bit of the end of its telomeres - this is because the machinery that runs along DNA falls off just before the end, leaving off the last bit of DNA from the new copy. Telomerase is responsible for adding a bit back on to the ends of the chromosome. Dr. Greider and her fellow Nobel laureates discovered this important enzyme and she's devoted her research to the study of telomerase since then. Despite telomerase's reparative properties, eventually telomeres are shortened after enough cell divisions (programmed cell death eliminates the cell at this point if all is working well!). This is because telomerase is limiting - there's just not enough of it to keep up with cell division. 

What happens when telomerase isn't present? The answer is completely fascinating! Dr. Greider talked about haplo-insufficiency - sometimes one copy of a gene isn't enough to produce enough enzyme. This is the case with telomerase. In families that are heterozygous for a mutation in the gene that encodes telomerase, telomeres shorten leading to a distinct disease. This disease affects younger and younger people with each generation in the family (i.e., affected grandfather develops the disease at 60, a father at 40, and a son at 20) - this is called genetic anticipation. Through studies using wild type and laboratory strains of mice, researchers have been able to model this disease. What they found was that even once the mutation was bred out of a generation, the mice that had two copies of telomerase still suffered from short telomeres. It took several generations for normal telomere length to reappear.

Thinking about the action of telomerase just brings up more and more questions! I can't wait to find time to read more about its implications in cancer. (Just think about how many times cancer cells divide.)  No wonder Dr. Greider has spent a career studying telomerase! Dr. Greider also connected her talk to the theme of this year's AAAS meeting, Science and Society, by talking about a model organism that I have a bit of a soft spot for: Tetrahymena thermophila. This tiny organism is chock full of chromosomes - on the order of 40,000. From this humble model organism, the researchers discovered an enzyme that may have big implications in a variety of human diseases and in aging.

This is the kind of talk that I came 3,000 miles to hear - it was so energizing to hear about Dr. Greider's work and exciting to think about the new discoveries that she and her fellow researchers may make in the coming years.