向 由起夫（むかい・ゆきお）
Yukio Mukai
職位：准教授
学位：工学博士（大阪大学）
●大阪大学大学院工学研究科博士後期課程修了
●大阪大学工学部助手、同大学院工学研究科助手を経て、テキサス大学M.D.アンダーソンがんセンターへ出張後、本学へ
専門分野
分子遺伝学、環境微生物学
研究テーマ
（1）酵母を用いた寿命制御機構の解明
酵母は単純な真核モデル生物として重要な研究材料です。酵母ノックアウトコレクションのメタボローム解析から新しい寿命遺伝子を探索し、寿命制御機構の解明に取り組んでいます。また、寿命を延ばす環境因子を探索しています。
（2）酵母を用いた転写抑制機構の解明
酵母 Tup1-Ssn6 タンパク質複合体は様々な遺伝子の転写を抑制するコリプレッサーです。Tup1とSsn6タンパク質の立体構造から、転写抑制に関与するアミノ酸残基を推定しています。それらの置換変異体の解析から、Tup1-Ssn6 による転写抑制機構を明らかにしていきます。
（3）アユ冷水病ワクチンの開発
琵琶湖産のアユが冷水病菌に感染していることが問題となっています。この問題を解決するために、アユ冷水病ワクチンの開発に取り組んでいます。冷水病菌が分泌するタンパク質をコードする遺伝子のクローニングと大量発現を行っています。
Topics of research
1．Molecular and genetic mechanisms for determination of life span in yeast
The budding yeast Saccharomyces cerevisiae is an important eukaryotic model organism. The yeast has been used to elucidate mechanisms for determination of cellular life span. I would like to know the genes that are related to life span and their function to regulate life span. Our group identified novel genes that regulate life span using metabolome analysis of yeast knock-out strains. We are comprehensively screening for long-lived or short-lived mutant strains. These works would facilitate finding compounds that extend life span.
2．Molecular and genetic mechanisms for transcriptional repression by Tup1-Ssn6 corepressor complex
The Tup1-Ssn6 corepressor complex of Saccharomyces cerevisiae is well-studied for elucidating mechanism of transcriptional repression. Tup1-Ssn6 is recruited to promoter regions of genes to repress their transcription. Two mechanisms for transcriptional repression by Tup1-Ssn6 are proposed. Tup1 interacts with transcriptional machinery including RNA polymerase to inhibit transcription. Tup1 also interacts with histones H3 and H4 to establish repressive chromatin structures. Crystal structure of Tup1 protein is used to predict amino-acid residues required for transcriptional repression. We are investigating the transcriptional repression activity of Tup1 mutant protein in vitro and in vivo.
3．Development of vaccine against coldwater disease in ayu
We have a serious problem of bacterial coldwater disease in ayu in Lake Biwa. To solve the problem, we are developing vaccine against the disease. Genome sequence of Flavobacterium psychrophilum which is infected to ayu was determined. These nucleotide sequence predicted the genes available for development of the vaccine. We focus on the genes encoding secreted proteins. These genes are cloned and expressed in E. coli or yeast as a candidate for vaccine.
主な業績論文等
- Mukai, Y., J. K. Davie, S. Y. R. Dent. Physical and functional interaction of the yeast corepressor Tup1 with mRNA 5'-triphosphatase. J. Biol. Chem. 278: 18895-18901. (2003)
- Widianto, D., E. Yamamoto, M. Sugiyama, Y. Mukai, Y. Kaneko, Y. Oshima, M. Nishizawa, S. Harashima. Creating a Saccharomyces cerevisiae haploid strain having 21 chromosomes. J. Biosci. Bioeng. 95: 89-94. (2003)
- Sakumoto, N., I. Matsuoka, Y. Mukai, N. Ogawa, Y. Kaneko, S. Harashima. A series of double disruptants for protein phosphatase genes in Saccharomyces cerevisiae and their phenotypic analysis. Yeast 19: 587- 599. (2002)
- Watson, A. D., D.G. Edmondson, J. R. Bone, Y. Mukai, Y. Yu, W. Du, D. J. Stillman, S. Y. Roth. Ssn6-Tup1 interacts with class I histone deacetylases required for repression. Genes Dev. 14: 2737-2744. (2000)
- Mukai Y., E. Matsuo, S. Y. Roth, S. Harashima. Conservation of histone binding and transcriptional repressor functions in a Schizosaccharomyces pombe Tup1p homolog. Mol. Cell. Biol. 19: 8461 (1999)
