International Collaboration in Chemistry: Investigation of Novel Telomeric Structures and Their Effects on Human Telomerase

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This International Collaboration in Chemistry (ICC) award in the Chemistry of Life Processes (CLP) program in the Division of Chemistry, with supplemental funds from NSF's Office of International Science and Engineering (OISE), supports work by Professor Hanbin Mao at Kent State University and Professor Hiroshi Sugiyama of Kyoto University, Japan, who is funded by the Japan Society for the Promotion of Science (JSPS), to carry out fundamental studies on the identification and characterization of novel structures in the human telomere regions. Located at the end of chromosomes, the telomere plays a critical role in cancers and senescence via DNA quadruplex structures that contain four DNA strands. Identification of novel structures other than quadruplexes is instrumental in understanding the fundamental processes of senescence and genesis of cancer. Single molecular techniques, such as laser tweezers and atomic force microscopy will be used to reveal the presence of the novel structures, to investigate the interaction of these structures with ligands, and to evaluate the effect of these structures on telomerase, an enzyme that maintains the telomere length. These methods will be complemented by molecular simulation and conventional bulk assays such as native gel electrophoresis, thermal denaturation, circular dichroism, and surface plasma resonance (SPR). The results from this three-year project, the broader impacts of which include the training of undergraduate and graduate students, can help to identify new therapeutic targets and agents to fight against diseases such as cancer.