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

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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.