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この度、熊本大学は、かねてより準備を進めておりました
「熊本大学 Better Co-being 社会を切り拓く異分野共創型博士イノベーター育成プログラム」
のホームページを公開する運びと相成りました。
当ホームページでは、プログラムについての最新情報及び募集案内を迅速かつ丁寧に発信してまいります。
今後とも、高い専門性と志を持つ人材の育成、また科学の発展のため、更なる情報の充実を図ってまいりますので、 どうぞよろしくお願いいたします。
令和6年度からの博士支援事業について、国立研究開発法人科学技術振興機構の公募事業「次世代研究者挑戦的研究プログラム」に本学が採択されました。
これを受け、令和6年4月から「Better Co-being社会を切り拓く異分野共創型博士イノベーター育成プログラム」を実施します。
選考に関する詳細な情報(募集要項)は近日中に公表しますが、選考に係るスケジュール概要と支援の内容については以下を予定しています。
(選考スケジュール)
4月上旬:募集要項公表
4月上旬~中旬:申請期間
5月上旬:面接審査
5月下旬:結果通知
6月中旬:初回の生活費相当額支給(4月~6月分)
(支援額)※国の施策・方針等で変更の可能性があります。
生活費相当額:20万円/月額
研究費:20万円/年額
プログラムの概要等、詳細は4月上旬公表予定の募集要項に掲載します。
Kumamoto University’s application to Support for Pioneering Research Initiated by the Next Generation (SPRING) for a doctoral support program from AY2024 has been accepted.
We will therefore be starting the Program for Fostering Innovators to Lead a Better Co-being Society (Better Co-being Program) from April 2024.
Detailed information on the selection process (application guidelines) will be announced shortly, but please find an outline of the selection schedule and details of the support below.
Selection Schedule
Early April: Release of application guidelines
Early to mid-April: Application period
Early May: Interviews
Late May: Notification of results
Mid-June: First payment of living expenses (for April to June)
Amount of support
(Subject to possible changes based on government policies and guidelines)
Living expenses: 200,000 yen/month
Research expenses: 200,000 yen/year
Further details will be published in the application guidelines which will be released in early April.
最先端研究セミナー
講演者: 香月 康宏 (鳥取大学医学部生命科学科 染色体医工学講座 教授)
日時: 2024年2月14日(水)12:30- 13:30
担当分野: ゲノム神経 塩田(内線:6633)
最先端研究セミナー
講演者: 酒井 寿郎 (東北大学大学院医学系研究科 分子代謝生理学分野 教授)
演題: Regulation of adipose thermogenesis and obesity via epigenomic reprogramming facilitated by a histone demethylase responsive to cold stress
日時: 2024年2月14日(水)10:30- 11:30
Abstract:
Lifestyle diseases, such as obesity, diabetes, hypertension, dyslipidemia, and heart and kidney diseases, are complex diseases influenced by both genetic and environmental factors. Epigenetic modifications, including DNA methylation and histone modifications like acetylation and methylation, play a crucial role in long-term adaptation to the environment. Inappropriate epigenetic memory is theorized to contribute to the development and worsening of lifestyle diseases. Research indicates that environmental stress can impact the epigenome.
JMJD1A, a histone demethylase, removes mono- and di-methyl groups from lysine-9 of histone 3, a modification known as H3K9 methylation, which is transcriptionally repressive. JMJD1A is involved in normal body weight control and adaptive thermogenesis, particularly in non-shivering thermogenesis in adipose tissue. Activation of JMJD1A occurs through β-adrenergic receptor signaling triggered by environmental stress such as cold exposure and excess calorie consumption. The phosphorylation of a specific serine residue at amino acid position 265 is crucial for JMJD1A activation.
JMJD1A’s histone demethylation activity is not essential for its role in β-adrenergic-dependent brown adipose tissue (BAT) activation. In this context, JMJD1A facilitates higher-order chromatin structural changes, promoting rapid gene transcription (1).. However, during the process of white adipose tissue (WAT) beiging, where cellular identity changes, JMJD1A’s histone demethylation activity becomes indispensable (2). In response to cold exposure and β-adrenergic stimulation, JMJD1A is phosphorylated at S265 and recruited to enhancer regions of thermogenic genes. It removes the repressive histone modification H3K9me2, enabling the expression of these genes. This two-step process involves signal sensing followed by epigenomic reprogramming (1, 2) (also reviewed in (3-5)). In this lecture, I will present our studies on environmentally regulated epigenomic reprogramming in adipocytes and discuss a potential strategy to prevent obesity and metabolic disorders based on this machinery.
References:
- Abe et al., JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis. Nat Commun 6, 7052 (2015).
- Abe et al., Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch. Nat Commun 9, 1566 (2018).
- Inagaki, J. Sakai, S. Kajimura, Transcriptional and epigenetic control of brown and beige adipose cell fate and function. Nat Rev Mol Cell Biol 17, 480-495 (2016).
- Matsumura, T. F. Osborne, J. Sakai, Epigenetic and environmental regulation of adipocyte function. Journal of Biochemistry 172, 9-16 (2022).
- Matsumura, F.-Y. Wei, J. Sakai, Epitranscriptomics in metabolic disease. Nat Metab 5, 370-384 (2023).
担当分野: 病態生化学 山縣(内線:5068)
最先端研究セミナー【医学・生命科学セミナー】
※医学教育部主催のセミナーです。最先端研究セミナーとして認定されます。
日程が変更となりました。
講演者: 石津 綾子(東京女子医科大学 顕微解剖・形態形成分野/教授)
演題: Hematopoietic stem cell regulation by extrinsic and metabolic factors
日時:2023年8月9日(水)17:30- → 2024年2月7日(水)17:30-
会場: 第2講義室(医学教育図書棟3階)
担当分野: 幹細胞ストレス学
※最新情報はこちらからご確認下さい。
最先端研究セミナー【医学・生命科学セミナー】
※医学教育部主催のセミナーです。最先端研究セミナーとして認定されます。
講演者: 岩井 一宏(京都大学 大学院医学研究科 細胞機能制御学/教授)
演題: Ubiquitin in signaling: a tale of atypical linear ubiquitin chains
日時:2024年1月31日(水)17:30-
会場: 第2講義室(医学教育図書棟3階)
担当分野: 造血・腫瘍制御学
※最新情報はこちらからご確認下さい。
最先端研究セミナー
講演者: 浅野 桂 (広島大学大学院統合生命研究科 特任教授)
日時: 2024年1月24日(水)12:00- 13:00
担当分野: 生殖発生 中村(内線:6557)
最先端研究セミナー
講演者: 角谷 徹仁 (東京大学大学院理学系研究科 教授)
日時: 2024年1月17日(水)12:00- 13:00
担当分野: 細胞医学 中尾(内線:6800)
最先端研究セミナー
講演者: 堤 尚孝 (岡山大学学術研究院医歯薬学域 (薬学系) 構造生物薬学分野 助教)
演題: Cryo-EM structure of the thrombopoietin-MPL receptor complex guides design of the cytokine variants that bias hematopoiesis
日時: 2024年1月10日(水)12:00- 13:00
Abstract:
Cytokines regulate the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) for blood cell homeostasis. Thrombopoietin (TPO) is one of the vital cytokines in HSC maintenance and a major factor responsible for megakaryopoiesis and platelet production in vivo (1). Abnormal activation of the TPO receptor (MPL) causes myeloproliferative neoplasms, while impaired function leads to thrombocytopenia and aplastic anemia (2). Furthermore, the TPO-MPL signaling is important for ex vivo HSC expansion aimed at bone marrow transplantation and gene therapy (3). Despite the clinical importance of MPL signaling, the structural mechanism of TPO-induced MPL activation was not elucidated due to the difficulty of producing the recombinant MPL.
We purified TPO bound to two chains of detergent-solubilized MPLs from HEK293 cells and visualized the extracellular region of the signaling complex by cryo-electron microscopy (4). In the structure, the TPO:MPL interfaces were clearly resolved, enabling the design of TPO mutants that would alter the stability of the receptor dimers. We screened cell growth and intracellular signaling induced by TPO mutants and found partial agonistic TPO variants activate specific downstream signaling pathways more selectively than the wild-type. We then probed the functional outcomes of these mutations on cells and in mice, demonstrating that the partial agonists could separate the two conflicting functions of TPO, HSC maintenance and myeloid cell differentiation, to some extent. The results indicate the potential utility of the modified TPO in fine control of platelet production in the difficult cases of immune thrombocytopenia (5) and clinical HSC transplantation in conjunction with the state-of-the-art HSC expansion protocols (6).
Reference:
1. C. C. Zhang, H. F. Lodish, Cytokines regulating hematopoietic stem cell function. Curr Opin Hematol 15, 307-311 (2008).
2. P. Guglielmelli, L. Calabresi, The MPL mutation. Int Rev Cell Mol Biol 365, 163-178 (2021).
3. J. A. Rubio-Lara et al., Expanding hematopoietic stem cell ex vivo: recent advances and technical considerations. Exp Hematol 125-126, 6-15 (2023).
4. N. Tsutsumi et al., Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis. Cell 186, 4189-4203.e4122 (2023).
5. W. Ghanima et al., Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica 99, 937-944 (2014).
6. M. Sakurai et al., Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature 615, 127-133 (2023).
担当分野: 組織幹細胞 小川(内線:6591)
最先端研究セミナー
講演者: 遠山 祐典(Principal Investigator, Mechanobiology Institute, National University of Singapore)
演題: Harnessing mechanics: Apoptosis and its mechanical role in cell fate determination
日時: 2023年12月20日(水)12:00- 13:00
Abstract:
Apoptosis, also known as programmed cell death, is a crucial mechanism that ensures the removal of unnecessary or damaged cells during embryonic development, tissue homeostasis, and certain pathological conditions. When a cell undergoes apoptosis within a tissue, it is extruded from its neighboring non-dying cells. Numerous laboratories, including our own, have demonstrated that cell extrusion is facilitated by the formation and contraction of actomyosin cables in the dying and neighboring cells [1-5]. This process leads to changes in mechanical tension in the neighboring cells. However, the way this modulation of tissue tension in the non-dying neighboring cells influences their own cellular function and cell fate remains largely unknown.
In this talk, I will present our latest findings regarding how mechanical tension in the surrounding tissue is altered in a wavelike manner as a result of apoptosis, as well as how this propagation of forces triggers cell cycle progression and proliferation in the neighboring cells [6]. If time permits, I will also share our unpublished results, which shed light on the involvement of immune cells in the process of apoptotic cell extrusion.
Reference:
[1] Thomas M, Ladoux B, Toyama Y*. “Desmosomal junctions govern tissue integrity and actomyosin contractility in apoptotic cell extrusion” Current Biology 26, 2942-50 (2020)
[2] Saw TB, Doostmohammadi A, Nier V, Kocgozlu L, Thampi S, Toyama Y, Marcq P, Lim CT, Yeomans JM, Ladoux B. “Topological defects in epithelia govern cell death and extrusion” Nature, 544, 212–216 (2017)
[3] Teng X, Qin L, Le Borgne R, Toyama Y*. “Remodeling of adhesion and modulation of mechanical tensile forces during apoptosis in Drosophila epithelium.” Development 144, 95-105 (2017)
[4] Kocgozlu L, Saw TB, Le AP, Yow I, Shagirov M, Wong E, Mège RM, Lim CT, Toyama Y*, Ladoux B*. “Epithelial cell packing induces distinct modes of cell extrusions” Current Biology 26, 2942-50 (2016)
[5] Toyama, Y, Peralta, XG, Wells, AR, Kiehart, DP, Edwards, GS. “Apoptotic force and tissue dynamics during Drosophila embryogenesis” Science 321, 1683-1686 (2008).
[6] Kawaue T, Yow I, Pan Y, Le AP, Lou Y, Loberas M, Shagirov M, Teng X, Prost J, Hiraiwa T, Ladoux B, Toyama Y*. “Inhomogeneous mechanotransduction defines the spatial pattern of apoptosis-induced compensatory proliferation” Developmental Cell, 58, 267–277 (2023)
担当分野: 形態制御 進藤(内線:6578)
最先端研究セミナー
講演者: 大森 司(自治医科大学医学部 生化学講座 病態生化学部門 教授)
演題: 遺伝性血栓・出血性疾患に対する遺伝子治療・ゲノム編集治療」
日時: 2023年12月19日(火)15:00- 16:00
場所:奥窪記念ホール (臨床医学教育研究センター 1階)
Abstract:
近年、先天性の難治性疾患に対する新たなドラックモダリティとして、遺伝子治療やゲノム編集が注目されている。既に国内においても、脊髄性筋萎縮症(SMA)に対するアデノ随伴ウイルス(AAV)ベクターをもちいた遺伝子治療薬が承認され、実臨床で利用されるようになった。また、先天性の血液凝固因子欠乏症である血友病に関してもEMAやFDAの承認を得たAAVベクター製剤も登場した。さらに、ゲノム編集治療も実際にヒトを対象とした臨床試験が欧米でおこなわれ、有望な成績が報告されつつある。本セミナーでは、近年著しい進歩を遂げている遺伝子治療やゲノム編集治療について一般論を概説するとともに、自身の研究室の成果である血友病やプロテインC欠損症に対する遺伝子治療やゲノム編集の基礎研究について最近のデータを紹介したい。現在、製薬会社の標的は、低分子化合物からバイオ医薬品への開発に大きくシフトしている。現在、国内のバイオ医薬品の貿易収支は3兆円/年を超える赤字となり、今後も、この傾向は続くことが予測される。国内産業の活性化、日本がグローバル化の波に追いつくためにも、希少難治性疾患を標的とした治療法の開発を積極的に行い、産官学連携を介した新たな創薬を行う必要性があると痛感している。
Recently, gene therapy and genome editing have attracted attention as new drug modalities for the treatment of congenital diseases. An adeno-associated virus (AAV) vector-based gene therapy drug for spinal muscular atrophy has been approved in Japan and is now in clinical use. AAV vector-based drugs for hemophilia have also recently been approved by EMA and FDA. In addition, genome editing treatments are now being tested in clinical trials. In this seminar, I will give a general overview of gene therapy and genome editing therapy and introduce recent data on basic research of gene therapy and genome editing treatment in our laboratory. Currently, the drug targets have largely shifted from small molecule compounds to biologics. Japan’s annual biopharmaceutical trade deficit exceeds 3 trillion yen, and this trend is expected to continue in the future. To revitalize the domestic industry and keep up with the wave of globalization, we need to actively develop treatments targeting rare intractable diseases and create new drugs by cooperating with industry, government and academia.
Reference (2022~2023)
- Hiramoto T, et al. Blood Advances (in press).
- Hino T, et al. Cell 2023;186:4920-4935.
- Kashiwakura Y, et al. Molecular Therapy – Methods & Clinical Development 2023:30;502-514.
- Hiramoto T, et al. Communications Medicine 2023;3:56.
- Baatartsogt N, J Gene Med. 2023 Mar 27:e3505.
- Kashiwakura Y., et al. Methods in Molecular Biology 2023;2637;195-211.
- Kashiwakura Y, et al. Molecular Therapy – Methods & Clinical Development 2022;27:404-414.
- Ishikawa H., et al. Scientific Reports 2022;12:11634
- Reiss UM, et al. Haemophilia 2022;28:61-67.
担当分野: 幹細胞誘導 江良(内線:6589)