Measurement and modulation of mechanical force transduction in living cells

在体内，细胞不断受到来自肌肉、空气和血流收缩的机械力以及来自有丝分裂和迁移的细胞力的作用。此外，细胞微环境的机械特性已被证明对干细胞的命运、恶性转化、肌生成和有丝分裂具有直接影响。细胞生物学的这些方面相对较新，尽管微环境和机械力的机械特性与细胞生物学有关，但细胞力转导和反应途径的潜在机制仍不清楚。在这个研究项目中，我们将深入研究控制机械力的转导和产生的物理和分子机制。利用最先进的生物物理学和遗传学方法，我们将开发一个机械的三维结构功能的早期变形和重塑过程的细胞响应机械力在真实的时间的理解。利用仅在Pelling实验室可用的技术，我们将能够通过在世界一流的培训环境中研究细胞生物学的这些新方面来解决知识差距。对基础设施的大量投资，以建立一个高度综合的跨学科培训环境，将使高素质的人员（HQP）学习细胞/分子生物学，显微镜，图像分析/计算和生物物理学的理论和实践方面。HQP将在跨学科实验室内工作和合作，为学术界或工业界的未来职业生涯获得高度可转移的技能。精通生物学和物理学语言的HQP是这项研究计划的目标以及这项工作的任何最终下游应用的核心，这些应用可能包括疾病的早期机械检测，生物途径的激活和控制细胞行为。

In-vivo, cells are constantly subjected to mechanical forces from the contraction of muscle, air and blood flow as well as cellular forces arising from mitosis and migration. Furthermore, the mechanical properties of the cellular micro-environment have been shown to have direct consequences on the fate of stem cells, malignant transformation, myogenesis and mitosis. These aspects of cell biology are relatively new and although mechanical properties of the micro-environment and mechanical forces are linked to cell biology, the underlying mechanisms of cellular force transduction and response pathways remain unclear. In this research program, we will delve into the physical and molecular mechanisms which govern the transduction and generation of mechanical forces. Utilizing state of the art biophysical and genetic approaches we will develop a mechanistic 3D structure-function understanding of the early deformation and remodelling processes of the cell in response to mechanical force in real time. Taking advantage of technologies only available in the Pelling Lab, we will be able to address a gap in knowledge by investigating these new aspects of cell biology in a world class training environment. The heavy investment in infrastructure to establish a highly integrated interdisciplinary training environment will enable highly qualified personnel (HQP) to learn the theoretical and practical aspects of cell/molecular biology, microscopy, image analysis/computation and biophysics. HQP will work and collaborate within an interdisciplinary laboratory, gaining highly transferable skills for later careers in academia or industry. HQP who are fluent in the languages of biology and physics are central to the objectives of this research program as well as any eventual downstream applications of this work which may range in applications from the early mechanical detection of diseases, activation of biological pathways and controlling cell behaviour.