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K-State Today

April 13, 2017



Undergraduate students study yeast ribosomes to reveal a fundamental process of cancer formation

By Katsura Asano

Asano lab undergraduates

Outside of commercial brewing, many people see yeast as a pesky annoyance rather than opportunity. Research in Katsura Asano's laboratory at Kansas State University uses these small organisms to help better understand some components of human life — more specifically, what goes wrong in cancerous cells.

The international consortium led by Asano, professor in the Division of Biology, renowned for his work with yeast, has recently published a peer-reviewed article, "Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5" in the high-impact journal, Cell Reports. Contributions from K-State include Chingakham Ranjit Singh, research assistant professor; Hiroyuki Hiraishi, the former research associate; and six undergraduate students.

Other co-authors on the study include scientists from the University of Kansas, Harvard Medical School, National Institute of Child Health and Development, National Institutes of Health, and Shimane University and Kyoto University, Japan. 

The goal of the Asano lab is to understand how protein synthesis is accurately initiated and how the process is dysregulated in cancer. The main focus of the published work looks at the mechanics of a piece of cellular machinery involved in protein synthesis: the ribosome.

Yeast cells at first glance do not appear like they would share any correlation with humans, but they actually utilize very similar mechanisms at the cellular level. This is especially true of the ribosomes and associated proteins in these two organisms. The process the ribosome goes through to start protein synthesis in certain yeast mutants has been linked to the process used by human ribosomes in cancer. Overall, the more that is discovered about this piece of machinery, the easier it will be to manipulate cells and potentially protect against certain pathologies including cancer. The article revealed the mechanistics of key parts of the machinery crucial for accurate start of protein synthesis.

The research in the article was initiated through top-of-the-line, modern and cutting-edge technology, including nuclear magnetic resonance and cryo-electron microscope. Several undergraduate scientists contributed to the biological verification works through yeast genetics.  

Chelsea Moore, senior in microbiology, performed several yeast assays to improve the outcome. Her results are featured in the publication. 

"When you're performing each experiment," Moore said, "you always have in the back of your mind the possibility that the results might be published. When those thoughts come to fruition it is quite a rewarding feeling."

Eric Aube, junior in medical biochemistry, and Ian Harmon, senior in biology, also saw their results in the paper.

"Watching the work that you did in collaboration with others lead to a major discovery makes all of the hours and struggles worthwhile," Aube said.

"It is highly rewarding to see the knowledge base you build during undergraduate years transform into something tangible. This project has allowed all of us to expand our understanding and further develop our appreciation for research," Harmon said.

Moore recently presented her work in a scientific meeting in Cold Spring Harbor, New York.

"Through work in the Asano lab I've had the opportunity to make connections in the scientific community. I'm definitely thankful that Dr. Asano guides us to sterile, safe and important lifelong lab techniques," Moore said.

Asano also places a high importance on collaborative learning both within the lab and with other labs. In part, through interaction with visiting international students, students in the Asano lab have made a great deal of contributions to successful peer-reviewed articles and projects.

In the cellular process called translation, the ribosome uses a three-letter genetic code or "codon" to produce each unit of proteins. The start codon to initiate protein synthesis is always "AUG". Non-AUG initiation can occur at start codons that differ by one letter such as CUG or GUG. This is rare in human translation but it does occur, especially when normal cells are challenged by cancer-forming perturbations.

Asano hopes his work will serve as a foundation for understanding a new way of tumorigenesis — the production of cancers — through a system of non-AUG translation.

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