In the Bustamante lab, I will explore how RNAs fold as they are being synthesized. To function properly, many linear RNA molecules must fold into a specific three-dimensional shape. For example, telomerase, an enzyme that helps maintain the ends of chromosomes, includes an RNA that is integral to its function; mutations that disrupt the structure of this RNA—including those associated with blood disorders such as aplastic anemia—abolish the enzyme’s activity. The process of RNA folding has been difficult to study, however, because it takes place as the RNA is being made. Now, combining sophisticated techniques in molecular genetics and biochemistry with a state-of-the-art method for observing the real-time behavior of individual molecules, I will watch single molecules of telomerase RNA fold as they are being produced and assess how their speed of manufacture or disease-associated mutations in their sequence alter the folding pathway or generate misfolded structures. I will also determine whether short nucleotide segments designed to bind to telomerase RNA can be used to purposely derail its folding process. Together, these findings could lead to novel treatment for anemias in which telomerase is shut down or cancers in which telomerase is inappropriately activated.