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RNA Technologies for Next Generation Medicine

TSUKAHARA Lab.
Professor:TSUKAHARA Toshifumi

E-mail:
[Research areas]Biochemistry and Molecular Biology
[Keywords]RNA splicing, RNA editing, Gene Expression, Genetic-code Restoration

Skills and background we are looking for in prospective students

To be interested in wonders of living things.
Sustainability to continue research even if failing the experiment. Motivation to contribute to future medical care.

What you can expect to learn in this laboratory

We are acquiring mammalian cell cultivation technology, gene isolation / analysis technology, genetic recombination technology and others. You can learn the technology to actually express genes, genetically engineer them, express them using E. coli and cultured cells, artificially mutate genes, and create artificial enzymes.

【Job category of graduates】
Cosmetics company ・ R & D worker, pharmaceutical company ・ development worker, chemical manufacturing company ・ research development company, patent attorney etc.

Research outline


Fig1. Base substitutions by RNA editing


Fig.2 Schematic representation of
artifitian RNA editing enzyme system

In our laboratory, we are conducting research mainly on biomolecules, especially RNA, from the viewpoint that biomolecules and cells are also materials. As a result of the human genome project, entire nucleotide sequence of human genes was elucidated.
The number of human genes is presumed to be less than 25,000. On the other hand, it is said that there are at least 200,000 kinds of proteins. Why are the types of proteins overwhelmingly larger than the number of genes? One of the clue is alternative splicing and RNA editing. Alternative splicing and RNA editing allows organisms to generate multiple mRNAs from a single genomic gene.

We are conducting research on intracellular RNA using microarray, real-time PCR, intracellular splicing analysis by gene transfer, and analysis of RNA metabolic intermediates. By comprehensively and precisely analyzing of the mRNAduring differntiation and drvelopment, we iwouuld like to dentify key genes in developmemt.

In addition, we are also carrying out researches on new treatments for diseases using our knowledge on RNA. Mutation in the gene may not be able to successfully produce the protein, which may also cause various diseases. Then, can we restore mutated genes? We challenge this task and are also working on the development of new genetic disease treatment methods.
Our attempt is to generate a new-generation of genetic treatments, which directly works on the genes of the patient and repairs the mutated genes.

In this way, our laboratory utilizes the knowledge of RNA research and is working on research on next-generation disease treatment that acts directly on RNA to improve the function of RNA. Traditional gene therapy was a treatment that supplements genes that do not function with alternative genes. We are continuing our research aiming to establish a treatment to restore broken genes.

Key publications

  1. Site-directed RNA editing by adenosine deaminase acting on RNA (ADAR1) for correction of the genetic code in gene therapy, Md Thoufic Anam Azad, Sonali Bhakta, Toshifumi Tsukahara, Gene Therapy, 24, 779–786 (2017)
  2. Endogenous Multiple Exon Skipping and Back-splicing at the DMD Mutation Hotspot. Hitoshi Suzuki, Yoshitsugu Aoki, Toshiki Kameyama, Takashi Saito, Satoru Masuda, Jun Tanihata, Tetsuya Nagata, Akila Mayeda, Shin’ichi Takeda, Toshifumi Tsukahara, Int. J. Mol. Sci, 17(10), 1 (2016)
  3. Chemical RNA Editing for Genetic Restoration: The Relationship between the Structure and Deamination Efficiency of Carboxyvinyldeoxyuridine Oligodeoxynucleotides. Vu Thi Luyen, Nguyen Thi Kim Thanh, Md Thoufic Anam Azad, Hitoshi Suzuki, and Toshifumi Tsukahara, Chemical Biology & Drug Design, 87, 583-593, (2016)

Equipment

Applied Biosystems 3130xl Genetic Analyzer (DNA sequencer)
Affymetrix GeneChip Syetem
Stratagene Mx3000P (Real-time PCR)
Fujifilm LAS3000
Agilent 2100 Bioanalyzer
Equipments for mammalian tissue culture

Teaching policy

・Excellent research is the mother of the best education.
・Do research to aim to world-classes. “Publish in top journals.”
・Originality is important for research.
・It’s hard and fun, because no one had done before.
・Don’t matter experiences, but abilities are important.
・”Keeping one’s motivation” is also important ability.

[Website] URL:http://www.jaist.ac.jp/ms/labs/tsukahara-www/english/index.html

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