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

本国际化学合作奖由美国国家科学基金会国际科学与工程办公室（OISE）资助，由日本科学促进会（JSPS）资助，支持美国肯特州立大学毛汉斌教授和日本京都大学杉山浩教授的工作。开展人类端粒区新结构的鉴定和表征的基础研究。端粒位于染色体的末端，通过包含四条DNA链的DNA四重结构在癌症和衰老中起关键作用。鉴定除四联体外的新结构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被用来揭示新结构的存在，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的影响，端粒酶是一种维持端粒长度的酶。这些方法将由分子模拟和传统的批量分析（如天然凝胶电泳、热变性、圆二色性和表面等离子体共振（SPR））来补充。这个为期三年的项目，其更广泛的影响包括培养本科生和研究生，其结果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.