The DNA strands that constitute the human genome are capped by protein-DNA structures called telomeres. Much like the small piece of plastic at the end of a shoelace (called an aglet) that serves to prevent the lace from unraveling, telomeres help to maintain the structural integrity of the genome. It has long been appreciated that telomeres get shorter each time a cell divides. As telomeres get progressively shorter, they loose their ability to protect genetic information encoded in our DNA. Fortunately, in most cell types there are mechanisms in place to sense when a cell’s telomeres get too short, and an orchestrated response kicks in that halts cell growth. However, in certain cell types that must divide rapidly for extended periods of time (ie. stem cells), an enzyme called telomerase serves to maintain telomere length and in doing so permits continued cycles of cell division. In the early 1990’s, it was recognized that 90% of human cancers are telomerase positive, raising the exciting possibility of telomerase targeted cancer drugs. However, despite decades of continued research, the potential of telomerase-based cancer therapies has yet to be realized. Work in the Stone Research Group at the University of California, Santa Cruz’s Department of Chemistry and Biochemistry aims to elucidate the structural properties of the telomerase enzyme in order to provide a conceptual framework for future development of effective cancer drugs. During my presentation, I will review some of the basics of human telomere biology, followed by a more detailed discussion of my laboratory’s ongoing efforts to better understand the detailed behavior of the telomerase enzyme.