Science AMA Series: I am David Zappulla, from Johns Hopkins University. I research telomeres, the caps that protect the ends of chromosomes in eukaryotic organisms from baker’s yeast to humans. Ask Me Anything about the role of telomeres in aging and cancer AMA!

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Hi Reddit, I am David Zappulla, an NIH-funded researcher in the Department of Molecular Biology & Genetics at Johns Hopkins University’s School of Medicine. I am here so you can Ask Me Anything about telomeres, which protect the ends of chromosomes in eukaryotic organisms from baker’s yeast to humans, and the enzyme telomerase, which is dedicated to the critical job of replenishing eroded telomeres.

In order for a cell to divide into two, it must first make a copy of its genome. The genome of each cell is composed of linear chromosomes, from yeast to humans. Linearity poses a serious problem, since DNA polymerases cannot completely replicate ends. This end-replication problem must be addressed somehow, or else chromosomes whittle down with each cell-division cycle, ultimately causing cellular senescence and death.

The Nobel-prize-winning (https://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/) enzyme telomerase solves the end-replication problem by replenishing telomeres during the process of human reproduction, resulting in offspring with full lifespan potential. However, by adulthood, telomerase is no longer present in the cells of most tissues in the body, leading to progressive telomere shortening with age. In contrast, most cancer cells aberrantly regain telomerase expression, permitting dangerously unchecked cell-proliferation potential. Thus, at least conceptually, telomerase has represented a tantalizing potential drug target for treating cancer and/or promoting healthy longevity.

My lab is working to understand how telomerase maintains telomeres at the molecular level. My colleagues and I have just published a paper in Cell (http://www.cell.com/cell/abstract/S0092-8674(17)31450-2)http://www.cell.com/cell/fulltext/S0092-8674(17)31450-2) that includes discovery of the long-sought, three-dimensional structures for both of the complexes of proteins and RNA that physically recruit the telomerase enzyme to chromosome ends in yeast. These new structural insights — spurred my lab’s 2015 eLIFE article (https://elifesciences.org/articles/07750) — move us closer to understanding the molecular mechanism by which telomeric DNA is maintained by the telomerase RNA-protein complex in yeast. My lab’s ongoing study of the molecular mechanisms of telomerase function in the advantageously manipulable yeast organism helps to pave the way for better understanding telomere biology in humans, and hopefully also identifying interventions to improve our health.

I am excited to read and respond to your questions at 1 pm. Today, January 22!

">Science AMA Series: I am David Zappulla, from Johns Hopkins University. I research telomeres, the caps that protect the ends of chromosomes in eukaryotic organisms from baker’s yeast to humans. Ask Me Anything about the role of telomeres in aging and cancer AMA!