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

化学系生命过程化学（CLP）项目的国际化学合作（ICC）奖，由NSF国际科学与工程办公室（OISE）提供补充资金，支持肯特州立大学的Hanbin Mao教授和日本京都大学的Hiroshi Sugiyama教授的工作，后者由日本科学促进协会（JSPS）资助，开展关于人类端粒区域新结构的鉴定和表征的基础研究。 端粒位于染色体末端，通过包含四条DNA链的DNA四链体结构在癌症和衰老中起着关键作用。 除了四链体之外，新结构的鉴定有助于理解衰老和癌症发生的基本过程。 单分子技术，如激光镊子和原子力显微镜将用于揭示新结构的存在，研究这些结构与配体的相互作用，并评估这些结构对端粒酶（一种维持端粒长度的酶）的影响。 这些方法将补充分子模拟和传统的散装分析，如天然凝胶电泳，热变性，圆二色性，表面等离子体共振（SPR）。 这个为期三年的项目的结果，其更广泛的影响包括本科生和研究生的培训，可以帮助确定新的治疗靶点和药物，以对抗癌症等疾病。

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.