How is the cell “constructed?”
Revealing the design principles of the cell through a combination of experiments and computer simulations

An equation can be used to describe the movement of stars in the universe and that of a baseball. This is one of the beauties of science. Is there a simple principle that can explain complex phenomena, even in the fundamental unit of life, a cell?
Dr. Kimura considers cells as architectures, and he studies the mechanical bases and principles that determine their design by utilizing various techniques such as microscopic observation, genetical analysis, and computer simulation.

Feelings toward “Cell architecture”

A variety of organelles exist in cells, such as nuclei and mitochondria, and they are properly sized and positioned according to the size and type of a given cell. They are just like architectures that have been perfectly designed. The laboratory, Cell Architecture Laboratory, describes the research approach of Dr. Kimura.

“Throughout the process of evolution, cellular shapes have arrived at well-balanced designs holistically. Instead of focusing on a particular organelle or a molecule, I would like to understand the cell as a whole, and my feeling is described by the word “architecture,” says Dr. Kimura.
“Even a beautifully designed piece of architecture cannot stand, if it fails to meet mechanical standards. As cellular research typically lacks sufficient viewpoint of mechanical analysis, I aspired to be a part of this field.”
“When I was an undergraduate student, I read a book about urban planning, and it stated, ‘there is an order in cities, even though individuals arbitrarily build houses. Well-balanced cities are autonomously built as if they are cells.’ To tell you the truth, this was the reason I became interested in cells and wanted to use the word ‘architecture.’ “

I want to offer a simpler mechanism

One of Dr. Kimura’s achievements concerning the mechanics responsible for determining cellular designs is that he explained the mechanism that controls spindle length according to cellular size. He did this by calculating the physical force necessary to pull microtubules that are connected to spindles depending on the surface areas or shapes of cells.

• Close-up! Interview, VOL.1

In addition, Dr. Kimura also offered quantitative evidence indicating that the movement of substances within cells, as if by convection, can be explained only by the forces impacting the cell cortex based on the computational simulations of fluid.

• Close-up! Interview, VOL.10

Dr. Kimura explains, “I think many researchers have been thinking on some level that if a current is generated by the force impacting on the cell cortex, it may cause convection. With computational simulation, one can calculate what types of currents can be generated by forces of a given magnitude. Cells have very small volumes and their interiors are filled with fluid of a syrup-like consistency. However, the calculation method for hydrodynamics has already been established. Hence, we ran simulations taking viscosity into consideration, and the generated current agreed with the measurement data obtained from cell observations. In biology, it is common to identify molecules first, assuming that there should be some molecules responsible for a given effect. I think it was meaningful to demonstrate a method in which one creates a cell in a computer and reveal its mechanism.”

Research focusing on “pressure” is also ongoing

“When a cell divides into two cells, several patterns can be imagined for the alignment of the new cells. By combining simulation and experiments, I believe we can determine whether they divide vertically, as the cells are pushed from the sides or whether the outcomes of cell positioning are because of pressure from the surroundings,” explains Dr. Kimura.
“In addition, although chromosomes contained within cell nuclei likely move freely in a larger nucleus and hardly move in a smaller nucleus because they are tightly packed, no one has ever confirmed this. We have started to examine the degree of restriction that chromosomes experience through simulation.”
“In the field of molecular cell biology, many complex cellular regulation mechanisms by genes or certain molecules have been revealed. Instead of strict control through regulation, I think the order of cells can also be explained by something simpler; for example, cells and their components may move toward available space or go somewhere else because some pressure was applied. Many researchers may find the need to examine more strictly and specifically, but I feel satisfied when complicated matters are explained more simply. I may be little unusual as a cellular biologist,” he added.

“Training to think” learnt in the graduate program was the start as a researcher

“As my father was a University Professor, I have never felt strange, while living as a researcher, and it has never been a difficult decision. My current state is just an extension of doing what I liked.”

Dr. Kimura continues, “All I can say is that I have a happy life, and I have been blessed in meeting great people at crucial points, particularly my supervisor in the graduate program, Dr. Masami Horikoshi. He was different from me, as he made a conscious decision to become a researcher and was devoted to teaching. Under his supervision, I was strictly trained to become a researcher.
“What I learned was ‘how to think.’ For example, if one wants to show that ‘cells die when exposed to certain drugs, ‘how should one design such an experiment? At least two conditions, samples with and without the drug, are required. A positive control is also necessary to show that the drug itself is active. In addition, two samples are needed for each condition, just in case some cells die by accident, and three samples for each condition are more preferable because the data will contain a majority even when each sample contains the same number of live and dead cells. I was instructed to start an experiment only after completely imagining the outcome of the experiment and had many opportunities for such training.”

What I learned from my former teacher is still applicable when I supervise graduate students

“Design, execute, and complete one’s own experiment. I believe this is critical to raising a professional scientist, and I want my students to keep questioning whether they can think thoroughly by themselves. If one enjoys such processes, there is no better job than being a researcher.”

Science is fun and can be applicable to many fields

When I asked for recommended readings for young people, he chose several books from his bookshelf.

“I read Super Science High School Lectures written by my former teacher Dr. Horikoshi from time to time to remind myself of my first resolution. The Aesthetic Townscape and Hidden Order (by Yoshinobu Ashihara) introduced me to the concept of cell architecture research. In Tenchi: The Samurai Astronomer (by Tow Ubukata), I was impressed that people of Edo-period in Japan were interested in mathematics.
Moneyball (by Michael Lewis) is about a success story in which the types of baseball players needed for a successful team were determined by analyzing baseball statistically. The Physics of Wall Street (by James Owen Weatherall) is about the relationship between mathematical rules and stock prices. All these books convey the joy of thinking scientifically. I will be glad if you become familiar with science by reading these books.”

(Text translated based on the interview conducted by Yoshiko Tamura in August 2014)