First person – Masashi Nambu

Masashi Nambu

How would you explain the main findings of your paper in lay terms?

During cell division in somatic cells (mitosis), the number of chromosomes is maintained; however, during the formation of gametes (sperm or egg cell), the number of chromosomes is halved in a process called meiosis, as otherwise a child would have twice as many chromosomes as a parent. When chromosomes segregate to daughter cells, a structure on chromosomes, called the kinetochore, attaches to microtubules like a thread. However, the segregation mechanism that halves the number of chromosomes is not clear. Therefore, we focused on kinetochore state. We developed a novel method for direct evaluation of kinetochore association and found that cohesin, the ring that bundles chromosomes, as well as its regulators adjust kinetochore association.

Were there any specific challenges associated with this project? If so, how did you overcome them?

To study the function of Rec8 in kinetochore association, we used rec8 defective (rec8Δ) Schizosaccharomyces pombe cells. In this research, we also fused Rec8 and GFP to visualize the metaphase chromosome. However, chromosomes cannot be visualized by using Rec8–GFP in rec8Δ cells. To overcome this problem, we produced the fusion protein Hht1–Rec8F–mCherry. This fusion protein does not contain the conserved cohesin domain of Rec8, and is cleaved at Rec8F by separase in anaphase. Therefore, we were able to visualize the metaphase chromosomes without Rec8!

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

We describe that sister kinetochore and centromere cores are positioned separately in mitosis, while they associate with each other in meiosis I. And this association state is regulated by cohesin and its regulators, including Moa1 and Mrc1. It is thought that these regulators establish kinetochore and centromere core association through cohesin. However, we found that Moa might have a cohesin-independent function, since Moa1 alone significantly reduced sister kinetochore and centromere core separation in mitosis. This was quite shocking!

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

My supervisor was Dr Yamamoto. His great passion helped accelerate our understanding of kinetochore association. Moreover, he is very friendly, so we freely discussed how sister kinetochore association is regulated. His enthusiastic guidance changed my mindset from student to that of a researcher.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

I was middle school-age when I first took an interest in science, during a student experiment. I was fascinated by the ammonia fountain caused by the phenolphthalein–ammonia reaction.

The most interesting moment from my research was producing Hht1–Rec8F–mCherry, which was my first experiment in the Yamamoto lab. I was very happy to observe fluorescing chromosomes. I feel this was the starting point for me as a researcher.

What's next for you?

I have left academia already and work at a Research and Development department of a company. My work is still similar to research in academia. But I am happy to see a product of my company be useful and sold in a store.

Tell us something interesting about yourself that wouldn't be on your CV

I often write Japanese calligraphy, during which I feel that time moves slowly. It relaxes me so I forget daily worries. It is important for me to empty my head after research.