Takahiko Akematsu, PhD

Takahiko Akematsu, PhD

E-Mail: takahiko.akematsu@univie.ac.at
Department of Chromosome Biology

Project: "MONREMO" - Mechanisms of nuclear reprogramming in a eukaryotic model organism

The process of somatic death and germline development in sexually reproducing system is an inevitable program that was acquired in the early history of eukaryotic evolution and directly relates with a mystery of aging or senescence of the human body. Cancer, on the other hand, is characterized by initially normal somatic cells that acquire eternal life and youth, characterized by out-of-control cell growth, living as parasites in the body. A central question in cancer biology is, how does the soma deviate from the standard program upon becoming cancerous? Changes in the epigenome, represented by histone post-translational modification (hPTM) have been implicated in the abnormal nuclear reprogramming in the soma that is manifest in cancer, but the exact mechanism by which this occurs is unknown. In addition, the mechanisms that alter the epigenome in the normal nuclear reprogramming in the germline during sexual reproduction, the keystone to understanding the mechanism of cancer formation, is still largely unexplored due to the multicellular complexity of the human body, in which the germline and somatic cells are spatially isolated from each other.

My study investigates the fundamental mechanism that commits the germline to nuclear reprogramming and the consequent somatic death using the ciliate protozoan Tetrahymena thermophila as model biology system. The most significant advantage of the organism in this aim is that it maintains stably differentiated germline and somatic nuclear genomes in a single cytoplasm, without a cell membrane boundary. During sexual reproduction, various types of hPTMs are involved in the progeny nuclear development and somatic nuclear death carried out in the same cytoplasm. Tetrahymena, with its nuclear dualism, will be a powerful tool to effectively examine the molecular relationship between the two types of genome (nuclei), and will provide useful information to reveal the mechanisms that control the standard program and its relation to cancer. In particular, my study focuses on mechanisms that alter the hPTMs in response to DNA double strand breaks (DSB) that are induced in the haploid germline genome during post-meiotic stage, which in turn, relays its signal to activation of the progeny nuclear development somatic nuclear death machineries. This is a novel type of induced DSB and the essential role of this event suggests involvement of a DNA damage response potentially relevant to an anti-cancer effect in triggering the machineries including the nuclear reprogramming. I try to elucidate the mechanism with the molecular/genetic dissection, including studies of protein/protein and DNA/protein interactions to more fully elucidate signaling mechanisms.

Publications

  • Akematsu T, Fukuda Y, Garg J, Fillingham JS, Pearlman RE, Loidl J. Post-meiotic DNA double-strand breaks occur in Tetrahymena, and require Topoisomerase II and Spo11. Elife. 2017 Jun 16;6. pii: e26176. doi: 10.7554/eLife.26176.

  • Fukuda Y, Akematsu T, Attiq R, Chika Tada, Yutaka Nakai, Pearlman RE. Role of the cytosolic heat shock protein 70 Ssa5 in the ciliate protozoan Tetrahymena thermophila. Journal of Eukaryotic Microbiology (2015) DOI: 10.1111/jeu.12203.

  • Osada E, Akematsu T, Asano T, Endoh H. A novel mitochondrial nuclease-associated protein: A major executor of the programmed nuclear death in Tetrahymena thermophila. Biology of the Cell (2014) 106:97-109.

  • Akematsu T, Fukuda Y, Attiq R, Pearlman RE. Role of class III phosphatidylinositol 3-kinase during programmed nuclear death of Tetrahymena thermophila. Autophagy (2014) 10:209-25.

  • Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T et al. (more than 1,000 others) Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy (2012) 8:445-544.

  • Akematsu T, Kobayashi T, Osada E, Fukuda Y, Endoh H, Pearlman RE. Programmed nuclear death and its relation to apoptosis and autophagy during sexual reproduction in Tetrahymena thermophila. The Japanese Journal of Protozoology (2012) 45:1-15.

  • Akematsu T, Pearlman RE, Endoh H. Gigantic macroautophagy in programmed nuclear death of Tetrahymena thermophila. Autophagy (2010) 6:901-11.

  • Akematsu T, Endoh H. Role of apoptosis-inducing factor (AIF) in programmed nuclear death during conjugation in Tetrahymena thermophila. BMC Cell Biology (2010) 11:13.

  • Matsuoka T, Kondoh A, Sabashi K, Nagano N, Akematsu T, Kida A, Iino R. Role of Ca2+ and cAMP in a cell signaling pathway for resting cyst formation of ciliated protozoan Colpoda cucullus. Protistology (2009) 6:103-10.

  • Kida A, Akematsu T, Hayakawa H, Matsuoka T. Suppression effects of nutrients on Ca2+-induced encystment of Colpoda cucullus. Protistology (2009) 6:98-102.

  • Akematsu T, Matsuoka T. Chromatin extrusion in resting encystment of Colpoda cucullus: a possible involvement of apoptosis-like nuclear death. Cell Biology International (2008) 32:31-8.

  • Akematsu T, Matsuoka T. Excystment-inducing factors in the ciliated protozoan Colpoda cucullus: Hydrophobic peptides are involved in excystment induction. Acta Protozoologica (2007) 46:9-14.

  • Yamamoto K, Takada Y, Kida A, Akematsu T, Kotsuki H, Matsuoka T. Effects of scavengers for active oxygen species on photoresponse and photodynamic damages to a pigmented protozoan, Blepharisma. The Journal of Protozoology Research (2007) 17:1-8.

  • Maeda H, Akematsu T, Fukui R, Matsuoka T. Studies on the resting cyst of ciliated protozoan Colpoda cucullus: resistance to temperature and additional inducing factors for en-or excystment. The Journal of Protozoology Research (2005) 15:7-13.

  • Yamasaki C, Kida A, Akematsu T, Matsuoka T. Effect of components released from bacteria on encystment in ciliated protozoan Colpoda sp.. The Japanese Journal of Protozoology (2004) 37:111-7.