Giving back to society
with the output of
mathematical models

“What is life?” This is the eternal question that has been raised by bioscientists around the world, past and present, and the pursuit of the answer continues in our world even today.
In recent years, the field of life sciences has undergone surprisingly rapid changes and taken significant steps forward, including advancements in genome analysis and the birth of induced pluripotent stem (iPS) cells.
However, even such advancements in bioscience are built on a foundation of the results of quiet and steady fundamental research about individual cells and the dynamics of a single molecule.
One of the examples of such fundamental research is the establishment of mathematical models through systems biology, with a focus on cardiogenesis, being undertaken by Assistant Professor Hitomi Sano.

  Focusing on the heart, which changes dramatically without ever stopping

I specialize in systems biology, which is typically recognized as an academic field that seeks to understand life phenomena as a system. However, experts of this field have different research subjects and topics of interest. For this reason, the definition of “systems biology” itself differs depending on the expert. Nevertheless, this is precisely what we could describe as one of the characteristics of systems biology.

To me, systems biology is an academic discipline that takes cells as the subject of study, and explores the relationship between how the dynamics of the molecules such as metabolites and proteins and ions in cells maintain the functions of the cells. Hence, depending on the subject of study, there are also cases where we focus on how the dynamics of an organ contributes to the functioning of an individual, for example, to his/her health.

Specifically, I conduct research into the process in which the heart is created in the fetus of laboratory animals. The process in which a fetus, and the organs of a fetus, matures into the shape and size of an adult, is known as “development.” I focus on the study of cardiogenesis, or how the heart is developed. My interest lies in the systems of the organ that we call the “heart,” which plays the role of circulating blood around the entire body while undergoing dramatic changes in shape and size, yet never once coming to a stop.

  Describing and considering life phenomena and its changes through the use of mathematical formula

In systems biology, bio-simulation is used in various projects, including collaborative research.

Bio-simulation involves the process of numerical simulation, which describes life phenomena in the form of mathematical formula, and solves these formula using computer programs. Here, the manipulation of the constants and parameters of mathematical formula expresses the “changes” of all elements, including the environment and circumstances surrounding life phenomena.

For example, in the field of studies of the heart, which I am engaged in, it is possible to simulate changes in the environment surrounding the heart by describing the system and process of the development of the heart with a set of differential equations, then manipulating the constants and parameters included in that equation.

Depending on the simulation, it may be possible to hypothesize conditions that are difficult to observe in experiments, or to create situations that do not seem to be probable in reality. Through this process, we are then able to extract the parts that we need in order to conduct further experiments and measurements for finding out what we do not currently understand about cardiogenesis to begin with.

The process of narrowing down the number of hypothesis that should be validated through physiological experiments also helps us to save on research funds incurred in experimental studies, and could therefore be described as a form of “eco” experimentation.

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• Computer Simulation

  The mathematical formula used to describe a single cell that makes up the heart stretches over 30 A4-sized pages. Based on this, the development of the heart is simulated by changing the constants and parameters.

  The advantages and challenges of simulation

In tandem with significant improvements in the performance of computers, there has been a dramatic increase in the number of cases whereby numerical simulation is used to recreate life phenomena.

For example, the K Computer, a supercomputer jointly developed by RIKEN* and FUJITSU LIMITED, has made it possible to recreate the entire heart and its dynamics as-is. Previously, it had only been possible to recreate sections such as cells, tissues, and parts of the organ. This re-creation of the entire heart has been applied to studies of treatment methods and evaluations of the efficacy of drugs.
*Japanese research institution

Hence, the advantage of simulation lies in its ability to capture the whole picture of the subject through the manipulation of constants and parameters included in a mathematical formula, such as presenting a new hypothesis based on the assumption of every change in life phenomena, or taking a bird’s-eye view of the whole picture in order to extract problems that could not be identified before. Furthermore, the method has also drawn attention for its ability to keep economic costs low.

However, under current conditions, bio-simulation has not yet attained a degree of precision that allows it to replace experimentation completely. To begin with, changes that cannot be expressed as constants and parameters in a mathematical formula cannot be simulated. In addition, the results of simulation do not correspond to the results of experimentation in many cases. Our challenge for the future is to improve the expressive capability of mathematical models while comparing the results against findings obtained through physiological experiments.

  Building mathematical models of cardiogenesis