导师风采 Supervisor's Information

Research Interests

Mitochondria are key organelles within the cell involved in the production of ATP, serve as a hub for biological reactions, and regulate many aspects of cellular activity such as cell senescence (aging), cancer, and stressful conditions. Mitochondria are also very dynamic structures with fluctuating morphologic transitions in response to cellular and environmental perturbations. While there have been many studies investigating the pathways and conditions that alter mitochondrial morphology, the connection between these morphological changes and gene expression regulation is still a poorly explored question. How does changing mitochondrial morphology during aging, cancer, and stress impact gene regulation? How do mitochondria regulate mRNA localization and control translation in response to the metabolic needs of the cell?

Projects

1. Decipher the mechanistic basis of enhanced protein synthesis on the mitochondria surface 

2. Investigate how fluctuating mitochondrial morphology during stress and disease affects gene expression of yeast and mammalian cells 

3. Pursue application method from the understanding of fluctuating mitochondrial morphology, such as screening of anti-aging drugs

As a model system, we will study mRNA localization and mitochondrial morphology in budding yeast and mammalian cells using an interdisciplinary approach combining quantitative microscopy, computational modeling, biochemistry, and molecular genetics. By focusing on a systems-level view of gene expression, we will advance our understanding of how organelle morphology impacts the physiology of the cell. Our multi-pronged, quantitative approach toward mRNA and mitochondrial morphological measurements will also allow us to tackle questions about the spatial relationship between biomolecules and other organelles, such as the vacuole and endoplasmic reticulum.

September, 2021– present, Assistant Professor, Tsinghua Shenzhen International Graduate School, China; 

April, 2020 – August, 2021, Assistant Project Scientist with Dr. Brian Zid, University of California San Diego; 

December, 2016 – March, 2020, Postdoctoral Scholar with Dr. Brian Zid, University of California San Diego; 

April, 2016 – May, 2016, Visiting researcher with Dr. Robert Singer, Albert Einstein School of Medicine; 

March, 2014 – November, 2016, Postdoctoral Scholar with Dr. Susanne Rafelski (currently at Allen Institute for Cell Science), University of California Irvine;

March, 2014, Ph.D. in Pharmaceutical Sciences, Tohoku University, Japan, Advisor: Dr. Toshifumi Inada      

Thesis title: Analysis of molecular mechanism of No-Go Decay and Dom34:Hbs1 targeting mRNA

March, 2011, Master of Science, Nagoya University, Japan; 

Thesis title: Analysis of translational regulator Pab1p on non-translating mRNA 

March, 2009, Bachelor of Science, Nagoya University, Japan;

Mitochondria are key organelles within the cell involved in the production of ATP, serve as a hub for biological reactions, and regulate many aspects of cellular activity such as cell senescence (aging), cancer, and stressful conditions. Mitochondria are also very dynamic structures with fluctuating morphologic transitions in response to cellular and environmental perturbations. While there have been many studies investigating the pathways and conditions that alter mitochondrial morphology, the connection between these morphological changes and gene expression regulation is still a poorly explored question. How does changing mitochondrial morphology during aging, cancer, and stress impact gene regulation? How do mitochondria regulate mRNA localization and control translation in response to the metabolic needs of the cell?

1. Decipher the mechanistic basis of enhanced protein synthesis on the mitochondria surface 

2. Investigate how fluctuating mitochondrial morphology during stress and disease affects gene expression of yeast and mammalian cells 

3. Pursue application method from the understanding of fluctuating mitochondrial morphology, such as screening of anti-aging drugs

As a model system, we will study mRNA localization and mitochondrial morphology in budding yeast and mammalian cells using an interdisciplinary approach combining quantitative microscopy, computational modeling, biochemistry, and molecular genetics. By focusing on a systems-level view of gene expression, we will advance our understanding of how organelle morphology impacts the physiology of the cell. Our multi-pronged, quantitative approach toward mRNA and mitochondrial morphological measurements will also allow us to tackle questions about the spatial relationship between biomolecules and other organelles, such as the vacuole and endoplasmic reticulum.

[1] Tsuboi T*, Viana MP, Xu F, Yu J, Chanchani R, Arceo XG, Tutucci E, Choi J, Chen YS, Singer RH, Rafelski SM*, Zid BM*. Mitochondrial volume fraction and translation duration impact mitochondrial mRNA localization and protein synthesis. (2020) Elife, 9, e57814. [*co-correspondence authors] 

[2] Tsuboi T*, Leff J, Zid BM*. Post-transcriptional control of mitochondrial protein composition in changing environmental conditions. (2020) Biochem Soc Trans. BST20200250. [*co-correspondence authors] Review

[3] Tsuboi T, Yamazaki R, Nobuta R, Ikeuchi K, Makino S, Ohtaki A, Suzuki Y, Yoshihisa T, Trotta C, Inada T. The tRNA Splicing Endonuclease Complex Cleaves the Mitochondria-localized CBP1 mRNA. (2015) The Journal of Biological Chemistry, 290(26), 16021-16030.

[4] Izawa T, Tsuboi T, Kuroha K, Inada T, Nishikawa S, Endo T. Roles of dom34:hbs1 in nonstop protein clearance from translocators for normal organelle protein influx. (2012) Cell Reports, 2(3), 447-453

[5] Tsuboi T, Kuroha K, Kudo K, Makino S, Inoue E, Kashima I, Inada T. Dom34:hbs1 plays a general role in quality-control systems by dissociation of a stalled ribosome at the 3' end of aberrant mRNA. (2012) Molecular Cell, 46(4), 518-529.

[6] Tsuboi T, Inada T. Tethering of poly(A)-binding protein interferes with non-translated mRNA decay from the 5' end in yeast. (2010) The Journal of Biological Chemistry, 285(44), 33589-33601.

April, 2018 – March, 2021, Research Fellowship for Young Scientists (PD), Japan Society for the Promotion of Science (JSPS)

December, 2016 – November, 2017, Research Fellowship for Research Abroad, The Uehara Memorial Foundation

April, 2014 – March, 2016, Postdoctoral Fellowship for Research Abroad, Japan Society for the Promotion of Science (JSPS)

April, 2011 – March, 2014, Research Fellowship for Young Scientists (DC1), Japan Society for the Promotion of Science (JSPS)

September, 2019, 2019 National Postdoc Appreciation Week Nominee, University of California San Diego

December, 2015, 2015 Education Committee Travel Awards, American Society of Cell Biology 2015

November, 2013, 2014 Grant for Study Abroad, Mochida Memorial Foundation for Medical and Pharmaceutical Research

September, 2012, Poster Award (2012), EMBO | EMBL 2012 Symposia Quality Control – From Molecules to Organelles

September, 2010, Yeast genetics forum poster prize, The 43rd study meeting: Yeast Genetics Society of Japan

March, 2009, Graduate presentation award, Nagoya University Department of Science Division of Biological Science