ASU, Chinese scientists unlock secrets of the fountain of youth

May 4, 2014

Arizona State University scientists, together with collaborators from the Chinese Academy of Sciences in Shanghai, have published a first of its kind atomic level look at the enzyme telomerase that may unlock the secrets to the fountain of youth in the journal Nature Structural and Molecular Biology.

Telomeres and the enzyme telomerase have been in the medical news a lot recently, due to their connection with aging and cancer. Telomeres are found at the ends of our chromosomes and are stretches of DNA which protect our genetic data, make it possible for cells to divide and hold some secrets as to how we age – and also how we get cancer. Julian Chen and graduate student Dustin Rand conduct research at ASU Download Full Image

An analogy can be drawn between telomeres at the end of chromosomes and the plastic tips on shoelaces: the telomeres keep chromosome ends from fraying and sticking to each other, which would destroy or scramble our genetic information.

Each time one of our cells divides, its telomeres get shorter. When they get too short, the cell can no longer divide, and it becomes inactive or dies. This shortening process is associated with aging, cancer and a higher risk of death. The initial telomere lengths may differ between individuals. Clearly, size matters.

“Telomerase is crucial for telomere maintenance and genome integrity,” explains Julian Chen, professor of chemistry and biochemistry at ASU and one of the project’s senior authors. “Mutations that disrupt telomerase function have been linked to numerous human diseases that arise from telomere shortening and genome instability.”

Chen continues that, “Despite the strong medical applications, the mechanism for telomerase holoenzyme (the most important unit of the telomerase complex) assembly remains poorly understood. We are particularly excited about this research because it provides, for the first time, an atomic level description of the protein-RNA interaction in the vertebrate telomerase complex.”

The other senior author on the project is professor Ming Lei, who has recently relocated from the University of Michigan to Shanghai, China, to lead a new National Center for Protein Science (affiliated with the Chinese Academy of Sciences).

At its core, telomerase is composed of two principle components: 1) a catalytic protein which synthesizes DNA from a template located within and 2) an intrinsic RNA component.  Chen's laboratory has recently developed a means to highly purify an independently functional fragment of the telomerase protein.  This functional telomerase protein fragment is aptly termed, Telomerase RNA Binding Domain (TRBD) for its RNA binding function.  Additionally, Chen’s researchers employed their purified protein to determine the specific region within TRBD responsible for binding a fragment of the telomerase RNA component, termed CR4/5.

The collaboration with Lei's group enabled the two laboratories to generate highly pure TRBD protein and successfully assemble this with the CR4/5 RNA for X-ray crystallography.  X-ray crystallography involves bombarding the protein-RNA complex with high energy X-rays, which then scatter.  By interpreting the scatter pattern, Lei’s laboratory was able to determine the structure of the protein-RNA crystal, providing important insights into the binding of the RNA by the protein.  

The mysteries of telomerase protein and RNA assembly are beginning to be exposed, with the exhaustive work of researchers within the telomerase field.  The findings of professors Chen, Lei, and many others are improving our understanding of this fundamentally essential enzyme, slowly divulging its secrets which will be applied towards the development of therapeutics to enhance human health. 

The Department of Chemistry and Biochemistry in ASU's College of Liberal Arts and Sciences ranks 6th worldwide for research impact (gauged by the average cites per paper across the department for the decade ending in the 2011 International Year of Chemistry), and in the top eight nationally for research publications in the journals Science and Nature. The department’s strong record in interdisciplinary research is also evidenced by its 31st national ranking by the National Science Foundation in total and federally financed higher education research and development expenditures in chemistry.

This work was supported by grants from the US National Institutes of Health (RO1GM094450 to J.J.-L.C.), Ministry of Science and Technology of China (2013CB910400 to M.L.) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB08010201 to M.L.).

Jenny Green

Clinical associate professor, School of Molecular Sciences


Business school grad combines economics, math to create social value

May 5, 2014

Inspired by a sense of duty to the world, David Choi, a senior majoring in economics and supply chain management and mathematics at Arizona State University, is on a mission to tackle hunger and food security issues.

“With the help of structured thinking and decision-making, I hope to develop a skill set that can be useful in helping solve business and social problems,” said Choi. “For example, allocation of government resources to combat hunger can utilize mathematical models to optimize locations of food hubs and banks in food-scarce regions as a short-term solution, and offer incentives to farmers to facilitate better production and distribution of food in the long term.” portrait of David Choi Download Full Image

A Tempe native, David Choi graduated from Corona del Sol High School before applying to colleges, including ASU and several Ivy League universities. He chose ASU for its affordable world-class education, and took the bulk of his classes at ASU's W. P. Carey School of Business and College of Liberal Arts and Sciences.

At ASU, Choi has maintained exemplary grades in his dual business major with a 4.14 GPA. He has also served as head of the W. P. Carey Business Ambassadors program, which uses a select group of students as community liaisons. In addition, he has visited South Korea on the U.S. Federal Government’s David L. Boren Scholarship and worked as a research assistant in the W. P. Carey School’s Department of Supply Chain Management.

He has also been named a U.S. Presidential Scholar, National Merit Scholar, McCord Scholar and JPMorgan Chase Scholar, as well as an SAT Top Scorer, among other honors and awards. As a profitability intern at Boeing Company, Choi created, developed and implemented ideas for cost-saving improvements in the company’s production and supply chain. He also co-founded Onvard, a startup that focuses on online employee training.

“Before joining ASU, I wasn’t sure of the direction I wanted to take,” he said. “Being here has shaped me into the person I want to be. I’m never going to be a finished product, but am glad to be on the right path.”>

After graduation, the economics and supply chain management student plans to delve deeper into his topic of interest and will be joining a master’s degree program in management in science and engineering at Stanford University in California.

“I have always been intrigued by the way math and science impact decision-making,” he said. “The program will introduce me to the quantitative and qualitative models that can be utilized to become a better manager and decision-maker.”

Choi hopes to pursue management consulting as a career, with a focus on startups. He would eventually like to work on a doctoral degree in economics and become a professor.

“Having volunteered at food banks and witnessed the widespread hunger in low-income families, I would like to conduct research to aid economic development, especially in terms of food security,” he said. “I also want to teach because I’d be helping the next generation. I would have been through everything that my students are going through and help them along the way. I’d consider being able to conduct research on my topics of interest a bonus.”

Choi ultimately hopes to keep adding value to everything around him and improve the lives of others.

“The world’s an amazing place, and we rely on each other for social growth,” he said. “I think there is a sense of connectedness in adding social value to the world.”

Amy Hillman, dean of the W. P. Carey School of Business, said, “We are very proud of David’s accomplishments thus far and are confident that he’ll achieve his dreams, and in doing so, give back to so many.”

Media projects manager, Office of Knowledge Enterprise Development