Assoc.Prof. AKIYAMA Masahiro

Assoc.Prof. AKIYAMA Masahiro

Microbial Molecular Genetics

Please tell us about your own research and what you find interesting about it.

The molecular mechanisms of the DNA replication machinery are so well understood that they are described in basic biology textbooks. However, the dynamics of the replication machinery on chromosomes are not well understood, despite the fact that replication inhibition due to collisions between the replication machinery and the transcription machinery is a major cause of genome instability. We’re studying the basic principles of chromosome replication, and the mutations and genomic instability caused by their abnormalities using microorganisms. The replication machinery moves on the same chromosomal DNA as the transcription machinery dose. In microorganisms, the speed of the replication machinery on chromosome is close to that of the Japanese bullet train Nozomi, assuming that the speed of the transcription machinery is that of a slow-moving car. However, the microbial genome is accurately replicated without losing genetic information due to catastrophic events (mutation or genomic instability) caused by the collision between the fast replication and slow transcription machineries. That’s very mysterious. In addition, the lack of thymine, a substrate for DNA synthesis, logically inhibits movement of the DNA replication machinery anywhere on the chromosome, but certain genomic regions of an enterobacteria, E. coli, show strong genomic instability in thymine deficiency. The mechanism of this regional genomic instability is still a mystery.

Please tell us about the difficulties and joys of the research field.

In the study of DNA replication and mutation, there are almost no visual data such as micrographs that make you get the whole idea when you see with your eyes, so it’s difficult to create it only based on understanding, and when communicating the research content, I find difficulty in explaining it in words because of my limited verbal skill. However, with the advent of next-generation sequencers, we’ve entered a fun era in which DNA replication and mutation can be analyzed at the genome level.

Please tell us about the expected results and social significance of the project.

Thymine starvation death (technically called thymine-less death), which occurs when DNA replication is inhibited by a lack of thymine, a substrate for DNA synthesis, was discovered more than 60 years ago, but mechanisms of the cell death remain a mystery. The antibacterial agent trimethoprim and the anticancer drug fluorouracil (5-FU), which have been widely used in medical practice for many years, are drugs that cause this thymine starvation death. In our study of chromosome replication, we found that the E. coli genome is programmed to temporarily stop replication in a specific genomic region when thymine is in short supply, and that this region coincides with a genomic instability site specific for thymine starvation death. This study of the programmed replication arrest is expected to lead to the elucidation of the mechanism of thymine starvation death.

A message of support for students who are about to take the exam

Bravery and perseverance.

What websites, books, review articles, and so on, do you recommend for studying in order to apply for the lab ?
  • Essential Cell Biology, Chapter 5-6
  • Molecular Biology of the Gene, Watson et al., Cold Spring Harbor Laboratory Press
What do you do to keep yourself fresh?

I feel refreshed by watching movies on subscription services. I watch about 60 movies a year.