Disclaimer: machine translated by DeepL which may contain errors.
~ Message from a graduate student~.
Elucidation of the temporal characteristics of enzymes using mathematical models
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| Yuka Sekine |
| Department of Chemistry 2nd Year Doctoral Student |
| Birthplace Saitama, Japan |
| High School Urawa Girls' Upper Secondary School |
| Faculty Faculty of Science, Ochanomizu University |
When I was a high school student, I was vaguely interested in "living things" and belonged to the biology club. On the other hand, I was also interested in physics and mathematics, and I had a yearning to develop a robot that assisted human body movement. I had been wondering which field to pursue, but my intuition told me that it would be interesting if I could clarify life phenomena in detail from a systematic viewpoint, so I decided to study chemistry, which has a wide opening to various fields including physics and mathematics, and then to do research on biology. With this goal in mind, I took courses in the Department of Chemistry as my Department of Chemistry during my undergraduate studies, and also took courses in the Department of Biology. In the process, I developed a strong interest in proteins and other biomolecules that function inside cells. I was fascinated by the complex and elaborate mechanisms by which biological phenomena are controlled by networks of various molecules.
In graduate school, I am studying the temporal characteristics of the activation of enzymes that play a role in intracellular signal transduction. In addition to understanding life phenomena, the temporal characteristics of enzymes are also attracting attention in the treatment of diseases. For example, if the temporal changes in the activation of biomolecules involved in insulin action during insulin administration for the treatment of diabetes mellitus are known, it is expected to provide effective information for determining the administration interval at which insulin works more effectively.
In particular, I am studying three isoformsNote) of Akt, an enzyme that plays a central role in signal transduction. It has been suggested that each Akt isoform selectively regulates cellular functions by exhibiting unique temporal characteristics. However, there is no methodology to study the temporal characteristics of the three isoforms individually, and the details have not been clarified.
Therefore, we established a system in which the three isoforms can be examined individually using a light control method in which the activity of a specific molecule can be artificially manipulated by external light. By combining mathematical model analysis (so-called "dry"), we aim to elucidate the temporal characteristics of each isoform in detail, including information that cannot be obtained from biochemical experiments (so-called "wet") alone. Specifically, we will construct a model of the activation mechanism of each Akt isoform that incorporates the relevant signaling molecules, and obtain kinetic parameters by fitting the experimental values. The goal is to consider the biological significance of each parameter and to clarify in detail what is responsible for the differences in temporal characteristics between isoforms. Mathematical model analysis will allow us to quantitatively predict, for example, differences in the kinetics of intermolecular reactions and their relationship to cellular responses, which are difficult to determine experimentally, and will also help us to construct more effective experimental designs. I feel that the interest of my research lies in the fact that I can elucidate the details of the temporal activation mechanism of Akt isoforms, which have never been clarified before, by repeating hypothesis testing using wet and dry "two-pronged" approaches.
The activity of the three isoforms Akt1, Akt2, and Akt3 is regulated by an optical control method. We aim to analyze the temporal characteristics of the activation of each isoform measured experimentally by mathematical models, including the relationship with the cellular response.
I have had opportunities to discuss mathematical model analysis not only with members of my laboratory but also with professors from the Department of Physics. Although I am sometimes bewildered by the terminology and ideas of different fields, I feel happy when I obtain a clue that enables me to solve a previously unresolved problem from a new angle through discussion. I would like to continue to engage in discussions with a variety of researchers to become a researcher who can elucidate life phenomena in detail based on knowledge from various fields centering on chemistry.
(Note) Isoform: An isoform is a kind of subspecies that differs in some amino acid sequences. Isoforms show overlaps and differences in function and expression levels.