18th Grant

At the 47th Annual Meeting of the Molecular Biology Society of Japan held in Fukuoka, I gave an oral and poster presentation at a mini-symposium titled "Elucidation of the Dynamics of Gut Microbiota and Their Effects on the Host during Artificial Hibernation."

In recent years, it has been revealed that a state resembling artificial hibernation, characterized by a decrease in body temperature and oxygen consumption, can be induced by specifically stimulating Q neurons in the hypothalamus. In this study, to understand the dynamics of gut bacteria, which have a close relationship with the host, during artificial hibernation, we investigated changes in the gut microbiota and their effects on the host's metabolic functions, and I presented our findings.

At this conference, researchers from a wide range of fields, including molecular biology and neuroscience, gathered for lively cross-disciplinary discussions and exchanges of opinions on the latest research findings. During my oral and poster presentations, I was able to have vigorous discussions with researchers from various fields. I received feedback and advice from new perspectives that I had not encountered before, which I intend to apply to my future research. Additionally, I was greatly inspired by listening to many lectures and presentations.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support, which made my participation in this conference possible.

(Reina Miyajima, 1st-year Master's Student, Graduate School of Pharmaceutical Sciences)

I participated in the 18th Metabolome Symposium held in Tsuruoka City, Yamagata Prefecture, where I gave an oral and poster presentation titled "Exploration of Lipids Related to Gut Immunity Using Mass Spectrometry Imaging" and received the Young Investigator Award.

In recent years, it has become clear that the lipid composition of immune cells differs among subsets, but much remains unknown about their effects on immune function and their spatial regulation. In this study, to identify lipophilic metabolites related to gut immunity, we analyzed Peyer's patches using mass spectrometry imaging and clarified the distribution of lipids that correlate with the localization of immune cells. Furthermore, by analyzing mice deficient in a lipid metabolism enzyme, we identified one of the regulatory factors for these lipids.

Through this conference presentation, I realized the difficulty of concisely conveying my research content within a limited time. Thanks to repeated discussions with senior and junior lab members and professors, I was able to handle the Q&A session calmly on the day of the presentation, which I believe led to this award.

Also at this conference, I absorbed cutting-edge knowledge by listening to research presentations using the latest mass spectrometry technologies and actively participating in Q&A sessions. At the social gathering, I had the opportunity to speak directly with an expert in aging research and heard invaluable stories not only about research content but also about the motivations for starting the research and future prospects.

Finally, this conference presentation was made possible by a research encouragement grant from Sato Pharmaceutical Co., Ltd. I would like to take this opportunity to express my deepest gratitude.

(Taishi Hoshino, 6th-year Student, Department of Pharmacy, Faculty of Pharmacy)

I recently participated in the International Conference on the Bioscience of Lipids 2024, held in Taipei, Taiwan, where I gave a poster presentation titled "Probing Electrophilic Lipid Modifications in Phagocytic Macrophages with Chemical Biology."

Macrophages maintain tissue homeostasis by removing apoptotic cells through phagocytosis. Various metabolic fluctuations occur during the phagocytic process. Among these, highly reactive metabolites called Lipid-Derived Electrophiles (LDEs) are known to modify cysteine residues of intracellular proteins, but the overall picture of these post-translational modifications by LDEs is not clear. In this study, using a chemical biology method called Activity-Based Protein Profiling (ABPP), we comprehensively and quantitatively analyzed the modification state of cysteine in intracellular proteins. We successfully identified the target proteins of LDEs generated by 12/15-lipoxygenase, a phagocytosis-related enzyme highly expressed in mouse peritoneal macrophages. Among these, we focused on Cofilin-1, a cytoskeletal depolymerizing molecule. We observed in vitro inhibition of Cofilin-1 activity and enhancement of cellular phagocytosis by LDE treatment, suggesting that LDE modification regulates the physiological functions of macrophages.

By participating in the conference, I was able to learn important and up-to-date findings related to lipid research, which provided inspiration for my future studies. On the day of my presentation, I received opinions and questions from many professors, allowing me to consider my research from new perspectives and engage in lively discussions.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support, which enabled my participation in this conference.

(Kaiyuan Deng, 3rd-year Ph.D. program, Graduate School of Pharmaceutical Sciences)

I participated in the 3rd Korea-Japan Lipid Joint Symposium, held from May 21 to 23, 2024, in Busan, South Korea, where I gave an oral presentation titled "Functional Analysis of ACSL6 on Mitochondrial Homeostasis in Germ Cells."

Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid (LC-PUFA) crucial for spermatogenesis. Long-chain acyl-CoA synthetase 6 (Acsl6) is an enzyme that selectively metabolizes LC-PUFAs, including DHA, into LC-PUFA-CoAs, contributing to the production of DHA-containing phospholipids. It has been reported that in the germ cells of Acsl6-deficient mice, DHA-containing phospholipids are reduced, leading to infertility with abnormal spermatogenesis. However, the function of Acsl6 during the process of sperm differentiation was not clear. In this study, to elucidate the function of Acsl6 during sperm differentiation, we isolated germ cells at different differentiation stages and performed proteomics. As a result, we found that the expression of mitochondria-related proteins was decreased and the mitochondrial membrane potential was significantly reduced in the germ cells of Acsl6-deficient mice. Through this conference, I was able to have lively discussions about my research with the participants. I plan to use the comments I received to prepare for a future paper submission and to further develop my research. I would like to take this opportunity to express my deepest gratitude to Sato Pharmaceutical Co., Ltd. for their generous support for my participation and presentation at this conference.

(Ryuji Ota, 3rd-year Doctoral Programs, Graduate School of Pharmaceutical Sciences)

I participated in the 3rd Korea-Japan Lipid Joint Symposium held in Busan, South Korea, and gave an oral presentation titled "The Changes of Mitochondrial Membrane Lipids During Myoblast Differentiation and their Biological Significance."

It is known that mitochondrial function and morphology change significantly during the process of myocyte differentiation. Although it has been shown that the mitochondrial membrane lipid environment in myoblasts affects myocyte differentiation, there have been no detailed analyses of how mitochondrial membrane lipids change during this process. Therefore, this study aimed to clarify how mitochondrial membrane lipids change during myocyte differentiation and what effects these changes have. As a result, we found that with the differentiation of myoblasts, the linoleic acid (18:2) content of cardiolipin (CL), a phospholipid localized to the mitochondria, increases.

Through this conference, I was exposed to the latest information in lipid biology from both Korea and Japan, and by exchanging opinions with researchers, I was able to further deepen my understanding of my own research.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support for my participation in this conference.

(Chinami Fujiwara, 1st-year Master's Student, Graduate School of Pharmaceutical Sciences)

I participated in the International Federation of Placenta Associations 2024 (IFPA2024), held from September 3 to 6, 2024, at the DoubleTree by Hilton Montreal, and gave a research presentation titled "Effect of short-chain fatty acids on mouse abortion rate and immune cells in the placental decidua." Since its first meeting in 1995, IFPA has been held in various countries and regions. More than 10 participants from Japan attended IFPA2024, where lively discussions transcending national, regional, and research field boundaries took place.

The breakdown of immune tolerance in the placenta is suggested to be a cause of miscarriage. In particular, at the decidua, the boundary between the fetal-derived placenta and the maternal uterus, a decrease in regulatory T (Treg) cells is involved in miscarriage. Therefore, inducing decidual Treg cells could potentially prevent miscarriage. We focused on short-chain fatty acids, which are known to induce Treg cells, and evaluated their effects on decidual T cells and fetal resorption by administering them to a spontaneous abortion mouse model. At this conference, we were able to show that while the effect of short-chain fatty acids on decidual T cells in the spontaneous abortion mouse model was small, they may partially contribute to improving fetal resorption. I also attended the conference for its entire duration, actively listened to others' presentations, and deepened my understanding of the interactions of physiological substances between the placenta and other tissues, as well as the behavior and functional differences of decidual immune cells at different stages of pregnancy.

Overall, this conference was not only a valuable opportunity to present my research in English but also a very meaningful experience where I could learn new insights into placental research and presentation techniques from participants from other countries.

Finally, I would like to express my sincere gratitude to Sato Pharmaceutical Co., Ltd. for their generous support for my participation in this conference.

(Gaku Fukumori, 2nd-year Master's Student, Graduate School of Pharmaceutical Sciences)

I participated in the 30th ICMRBS conference held in Seoul, South Korea, and gave a poster presentation titled "14-3-3ζ Interacts with FOXO3a-DBD and Competitively Dissociates DNA through the Tethering Effects via Two Binding Motifs." In cancer cells, abnormally enhanced phosphorylation signals regulate transcription factors and translation regulators, leading to cancer cell proliferation. One of the transcription factors whose function is suppressed by phosphorylation signals is FOXO3a. FOXO3a is a transcriptional activator that induces the expression of apoptosis-related proteins, but in cancer cells, FOXO3a is phosphorylated and binds to the 14-3-3ζ protein, causing it to dissociate from DNA and lose its transcriptional activation ability. Until now, the mechanism by which the binding of 14-3-3ζ causes DNA to dissociate from phosphorylated FOXO3a had not been clarified. Therefore, we analyzed the interaction between phosphorylated FOXO3a and 14-3-3ζ using NMR and revealed that 14-3-3ζ competitively dissociates DNA.

By participating in this conference, I was not only able to discuss my research with researchers from around the world through my poster presentation, but I also deepened my knowledge by listening to cutting-edge research presentations using NMR.

Finally, I would like to express my deepest gratitude to Sato Pharmaceutical Co., Ltd. for their generous support, which made my participation in this conference possible.

(Shota Enomoto, 1st-year Master's Student, Graduate School of Pharmaceutical Sciences)

We presented our work on the development of a synthesis method for TriQuinoline (TQ) derivatives and its applications at the 29th International Society of Heterocyclic Chemistry congress, held from July 21 to 26, 2024, at the University of Aveiro in Portugal. In this study, we established an efficient derivative synthesis process, achieving the synthesis of a wide range of TQ derivatives in high yields. The successfully developed TQ derivatives can be used as G4 ligands with the ability to specifically bind to DNA G-quadruplexes (G4s) and are expected to be new tools in cancer therapy and gene regulation research. Furthermore, it was shown that these derivatives can also be applied as adsorbents for polycyclic aromatic hydrocarbons (PAHs), known environmental pollutants, and are anticipated as an innovative method for their removal.

In our presentation, we detailed the synthesis method for TQ derivatives, the structural characterization of the substances, and data on their G4 binding ability and PAH adsorption performance. The function as G4 ligands and the high efficiency of PAH removal were particularly well-received, attracting significant interest from attendees. The lively discussions provided new insights, and further development of this research is anticipated.

Finally, we would like to express our deep gratitude to Sato Pharmaceutical Co., Ltd. for their generous support in making this presentation possible. Without the funding provided by the company, achieving these results would have been difficult. Based on these findings, we will continue to advance our applied research, aiming for practical application in the medical and environmental fields.

(Taiga Karimata, 3rd-year Doctoral Programs, Graduate School of Pharmaceutical Sciences)

In July, I participated in NEURO2024, held at the Fukuoka International Congress Center, and gave a poster presentation titled "The Immune Checkpoint Molecule LAG-3 Regulates Microglial Activation."

Microglia, the immune cells of the central nervous system (CNS), are known to contribute to neuronal development and CNS homeostasis. On the other hand, in many neurological diseases, neuronal damage caused by excessive microglial activation has been reported to be involved in the onset and progression of the pathology. Therefore, I focused on immune checkpoint molecules as factors that could regulate the excessive activation of microglia. The results revealed that lymphocyte activation gene 3 (LAG-3), one of the immune checkpoint molecules, is expressed in activated microglia and regulates their activation by suppressing the STAT1 signaling pathway.

Many experts in neurological diseases and glial cells participated in this conference, and I was able to discuss the challenges and future directions of my research, as well as its clinical applications, with them. As this was a joint meeting with the Federation of Asian-Oceanian Neuroscience Societies, I also had the opportunity to interact with many international researchers, which helped improve my English presentation skills.

Finally, I would like to express my deepest gratitude to Sato Pharmaceutical Co., Ltd. for their generous support in the form of a research encouragement grant, which made my participation in this conference possible.

(Motoki Oshima, 2nd-year Master's Student, Graduate School of Pharmaceutical Sciences)