Towards a molecular mechanism for mechanosensitive gene regulation

寻找机械敏感基因调控的分子机制

• 批准号: 8471015
• 负责人: Benjamin L Ricca
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471015
• 关键词: Adhesives; Affect; Apoptosis; Atomic Force Microscopy; Behavior; Biochemistry; Biological Assay; Biological Process; Biophysics; Cell Count; Cell Culture Techniques; Cell physiology; Cells; Chromosome Mapping; Complex; Cytoskeleton; DNA biosynthesis; Development; Drug Targeting; Environment; Event; Feedback; Fibroblasts; Fluorescence Microscopy; Focal Adhesions; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic; Goals; Health; Hour; Image; Individual; Knowledge; Life; Link; Measures; Mechanics; Medical Technology; Mesenchymal Stem Cells; Messenger RNA; Methods; Molecular; Monitor; Nature; Neoplasm Metastasis; Output; Pattern; Pharmacotherapy; Physiologic pulse; Positioning Attribute; Process; Signal Transduction; Staging; Stimulus; Structure; Surface; Techniques; Testing; Time; Tissue Engineering; Tissues; Transcript; Transcriptional Regulation; United States National Institutes of Health; Work; cancer therapy; cantilever; design; experience; improved; insight; light microscopy; regenerative; regenerative therapy; research study; response; stem cell differentiation; therapeutic target; transcription factor; tumor; tumor progression

DESCRIPTION (provided by applicant): A cell's mechanical microenvironment an influence its behavior, from its adhesive and cytoskeletal structure to the genes it expresses, and has been shown to affect complex biological processes such as stem cell differentiation and tumor progression. However, the manner in which a cell measures and interprets mechanical information in its microenvironment, particularly transient mechanical signals such as those experienced during development and wounding, is unclear. The proposed work will explore these questions by directly imaging the accumulation of mRNA transcripts and transcription factor localization in live cells as the mechanical microenvironment is altered using force microscopy. In this way, we will be able to decipher the thresholds of mechanical stimuli, include stiffness changes or force changes, and the patterns of mechanical inputs, including continuous, oscillatory, and pulsed stimuli, that can elicit a genetic response, and vary the patterns of mechanical inputs to determine how a cell integrates transient short-timescale mechanical inputs into sustained long-timescale genetic responses, moving us toward a detailed mechanism for mechanosensitive gene regulation.

描述（由申请人提供）：细胞的机械微环境影响其行为，从其粘附和细胞骨架结构到其表达的基因，并且已显示影响复杂的生物学过程，如干细胞分化和肿瘤进展。然而，细胞在其微环境中测量和解释机械信息的方式，特别是瞬态机械信号，例如在发育和创伤期间经历的那些，尚不清楚。拟议的工作将探索这些问题，直接成像的mRNA转录本和转录因子的积累在活细胞中的机械微环境的改变，使用力显微镜。通过这种方式，我们将能够破译机械刺激的阈值，包括刚度变化或力的变化，以及机械输入的模式，包括连续，振荡和脉冲刺激，可以引起遗传反应，并改变机械输入的模式，以确定细胞如何将短暂的短时间尺度机械输入整合到持续的长时间尺度遗传反应中，使我们更深入地了解机械敏感基因调控的详细机制。