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Biochemist Awarded Top Research Grant from Japanese Government

March 3, 2014

Biochemist Awarded Top Research Grant from Japanese Government

Kotaro Nakanishi, assistant professor, chemistry and biochemistry, received a three-year PRESTO (Precursory Research for Embryonic Science and Technology) award, funded by the Japan Science and Technology Agency (JST) to initiate his research program. The grant is for $400,000 – 450,000 (depending on the rate of U.S.Dollars to Japanese Yen).

Nakanishi, who joined the Department of Chemistry and Biochemistry in August 2013, says he was drawn to Ohio State because he had received positive impressions of the university from attending several conferences, where he said, “I clearly remember that the quality of the presentations by the Ohio State students was quite good.”

JST gives junior faculty and postdoctoral-level young scientists an opportunity to develop their own project for three and a half years. Any Japanese scientist—even those working outside of Japan, or anyone who comes from a foreign country to work in Japan—is eligible for this grant.

“The Japanese Government chooses several themes such as green innovation, life innovation, nanotechnology and materials, and information and communications technology,” says Nakanishi.

“Each theme is further classified into a couple of divisions. I applied for the division of Structural Life Science and Advanced Core Technologies for Innovative Life Science Research.

“Since the PRESTO is one of the largest and most prestigious grants for junior faculty who are Japanese and/or work in Japan, I am very happy to have this opportunity. My area of RNA interference is an extremely competitive field, and thus this grant truly supports my research and allows me to set up expensive but essential instruments for crystallographers. I would like to dedicate myself to the project so that I will be able to contribute something exciting to my field as a member of Ohio State’s faculty.”

Nakanishi’s research group studies the structure of macromolecules in order to understand their mechanisms of recognition.

“Humans are able to recognize others through our five senses: sight, hearing, taste, smell and touch,” he explains. “Although the senses are sophisticated systems that allow us to understand objects, they sometimes lead us to misunderstandings. For example, we see a friend walking in front of us and say, ‘Hi John!’ But then we realize it is actually someone else.”

So, how about macromolecules in our body? Needless to say, they do not have eyes, ears, mouth or nose.

“But they behave as if they have a sense of touch to distinguish the right partner from others,” Nakanishi says.

“Touch itself seems to be a primitive but robust system to avoid such above-mentioned miscommunications. Macromolecules fully exploit their own structure designed for the specific shape of the substrate, inhibitor, other subunit, binding partner etc. They communicate with each other through their unique structures and unless the object snugly fits, macromolecules don’t acknowledge it as the proper one. Through the use of X-ray crystallography we can gain an understanding of how these structures determine events at the atomic resolution.”

The goal of Nakanishi’s research is to understand the molecular mechanism of microRNA biogenesis.

“The microRNA genes are encoded in genome and transcribed as non-coding RNAs that are not translated into protein. After processing by Drosha and Dicer, the ~22 nucleotide-length small RNAs are loaded into Argonaute protein as mature microRNAs and recruit the nucleoprotein complex to the target messenger RNAs dependently on the sequence complementarity.

“Since the discovery of posttranscriptional gene expression regulation by double-stranded RNAs, people have used the technique called gene silencing as a tool to reduce the expression level of interest genes. However, little is known about the molecular basis. Our group uses primarily X-ray crystallography to study how miRNAs are processed and exploited by the key enzymes of the RNA interference.”

Nakanishi received his BS degree from Tokyo University of Science in 2000 and an MS from the University of Tokyo in 2003. After working in industry, he returned to academic life and received his DSc in 2007 from Tokyo Institute of Technology, where he used X-ray crystallography and biochemistry to study aminoacyl-tRNA synthetase and the tRNA modification enzyme.

In 2008, he joined the laboratory of Dinshaw Patel at the Memorial Sloan-Kettering Cancer Center. His work there resulted in the determination of the crystal structures of Argonaute and Dicer. He was awarded the Japan Society for the Promotion of Science (JSPS) for Young Scientist, JSPS for Research Abroad and Human Frontier Science Program for Long-term Fellow.

In recognition of his work, Kotaro received the RNA Society/Scaringe Award in 2012 and the Young Scientists’ Prize of the Commendation for Science and Technology by the Japanese Minister of Education, Culture, Sports, Science and Technology in 2013.

--Sandi Rutkowski, Arts and Sciences Communications

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