International Collaboration in Chemistry: Population Dynamics and Subdomain Stability of Folded Species in the Full-length Overhang Region of Human Telomeres

化学部生命过程化学项目的国际化学合作奖支持肯特州立大学的Hanbin Mao博士研究端粒的工作，端粒是染色体末端的新DNA结构。 这项工作是与日本京都大学的Hiroshi Sugiyama博士合作完成的，他得到了日本科学促进协会的资助。 人类染色体的端粒区域参与生物衰老和肿瘤形成的过程。因此，对端粒的研究可以为治疗与年龄有关的疾病和癌症提供信息和促进其发展。 毛博士的研究目标是阐明人类端粒DNA中形成的G-四链体物种的机械化学性质和种群动力学。 为了实现这一目标，毛博士将同时使用现有的物理方法和实验室开发的新方法，每次研究一个分子。 合作研究的国际性为培养美国学生提供了独特的环境。 在日本的研究实验室的访问为学生创造了获得全球视野和获得协作技能的机会。 高中生将在毛博士的实验室参加研究，并准备参加高中科学竞赛和科学展览。端粒中形成的DNA G-四链体虽然非常重要，但由于端粒区域的长度和构象的多样性，很难进行研究。 这个复杂的结构问题可以使用研究人员实验室新开发的单分子方法来解决。 在肯特州立大学，光学镊子将被用来在亚分子水平上解剖G-四链体，方法是通过G-四链体单元内的特定位置进行机械展开。 另一方面，通过类似于生物学中的种群动力学的方法，可以在不同结构的解卷积之后重建G-四链体物种的种群分布。 在存在小分子的情况下评估这些群体概况可以使药物的开发成为可能，所述药物与端粒G-四链体相互作用，从而干扰各种生物过程。

This International Collaboration in Chemistry award from the Chemistry of Life Processes Program in the Chemistry Division supports the work of Dr. Hanbin Mao from Kent State University to study telomeres, which are new DNA structures present at the end of chromosomes. The work is done in collaboration with Dr. Hiroshi Sugiyama of Kyoto University, Japan, who is funded by the Japan Society for the Promotion of Science. The telomere regions of human chromosomes are involved in the processes of biological aging and tumor formation. Consequently the study of telomeres can inform and advance the quest for the treatment of age-related diseases and cancer. The goal of Dr. Mao's research is to elucidate the mechanochemical properties and population dynamics of the G-quadruplex species formed in a human telomeric DNA. To achieve this goal, Dr. Mao will use both existing physical methods as well as new methods developed in his lab for the study of one molecule at a time. The international character of the collaborative research offers a unique setting to train U.S. students. Visits of the research lab in Japan create the opportunity for the students to gain a global perspective and to acquire collaborative skills. High school students will participate in research in Dr. Mao's lab and will be prepared to participate in high school science competitions and scientific exhibitions.Although of fundamental importance, the DNA G-quadruplex formed in the telomeres is difficult to investigate given the length of the telomeric region and the diversity of conformations it can adopt. This complex structural problem can be addressed using single-molecule methods newly developed in the labs of the investigators. At Kent State, optical tweezers will be used to dissect G-quadruplexes at sub-molecular level by mechanical unfolding through specific locations inside a G-quadruplex unit. On the other hand, by an approach analogous to the population dynamics in Biology, the population profiles of G-quadruplex species can be reconstructed after deconvolution of different structures. Evaluation of these population profiles in the presence of small molecules could enable the development of drugs, which interact with telomeric G-quadruplexes and thus interfere with various biological processes.