旭硝子財団助成研究成果報告2024
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近藤 徹39Toru KONDO関口 寛人40Hiroto SEKIGUCHI1分子吸収分光法を用いた生体光反応の揺らぎ観測(2022採択)Fluctuation analysis of biological photoreaction using single-molecule absorption spectroscopy(Project 2022)革新的生体光操作技術の創出に向けたマイクロLED光神経プローブの開発(2022採択)Development of microLED neural probe for the innovation of biological optical manipulation technology(Project 2022)43と新原理を基盤とすることで,高効率・高生存率を実現可能な物理的細胞内封化技術「電動ナノ注射器」を開発することを研究目的とする.Cell therapy is a new medical treatment to treat diseases by transplanting functional cells after manufacturing, culturing, and evaluating cells in vitro. However, the cell types that can be used for treatment have been limit-ed due to restrictions in the substance delivery technology required for cell processing. To resolve such prob-lems, the applicant has developed a new metallic nanotube membrane for cell puncture, and has developed a nanostamping method to deliver exogenous cargoes into cells with high efficiency and high viability. The purpose of this research project is to develop an electric nano-injector that can achieve high efficiency and high survival rate, based on the applicant's new material and new principle.構造生物学的手法の目覚ましい発展により,生体系の詳細構造が原子分解能で明らかにされ,構造を基に生体反応機構を議論できるようになった.しかし,実際に生体系が機能する生理環境下では,熱的な揺らぎや反応に付随した構造変化により,反応系は絶えず変動している.特に,光合成光反応を制御する色素タンパク質では,分子近傍の局所的な構造変化や構造不均一が生じるだけでも光反応機能に大きく影響し得る.このような生体系の動態性と光反応過程の相関関係を明らかにするため,吸収検出をベースにした1分子分光法を開発した.フェムト秒パルスレーザーを用いた過渡吸収測定装置を構築し,光合成光反応系の1粒子分光解析に成功した.Remarkable advancements in structural biology techniques lead to the elucidation of detailed structures of biological systems at atomic resolution, enabling the discussion of biological reaction mechanisms based on structural information. However, in the actual physiological environment, structural fluctuations due to ther-mal motions and conformational changes in response to reactions continuously perturb the reaction systems. Particularly in photosynthetic pigment-proteins where light reactions are regulated, even local structural changes and structural heterogeneity in vicinity of pigment molecules can significantly influence the photore-action processes. To reveal the correlation between the dynamics of biological systems and the photoreaction processes, we developed a single-molecule spectroscopy based on the absorption detection. By constructing a transient absorption microscope using a femtosecond pulse laser, we succeeded in single-particle spectro-scopic analysis of photosynthetic light reaction systems.脳機能の統合的理解に向けて,時空間特異的に細胞の活動状態を操作することが求められている.光遺伝学に基づく細胞操作技術は高い時空間分解能で神経活動を制御できるため神経科学研究において重要な役割を果たしてきたが,より複雑な生体統合システムの理解をさらに深めるには多点での生体光照射や薬理学的操作との組み合わせが求められる.本研究では,マイクロLED集積技術を基盤にして,生体

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