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物理和天文学论文答辩-查德·霍布森

3月17日下午1点-下午三点

北卡罗来纳大学ch分校物理和天文学论文答辩

乍得霍布森

“关于细胞核的生物力学:综合力和光学介绍的见解”

细胞核是多功能的。它们不仅可以容纳并保护基因组,而且它们还为周围细胞提供了机械稳定性,并将细胞外机械提示转化为生化反应。例如,在细胞表面的整合蛋白上施加的力通过细胞骨架和核传播到核中,导致染色质和转录上调的局部拉伸。然而,核的机械完整性通常在一系列疾病中遭受损害,从癌症到层状病变。这些疾病对特定核成分具有靶向影响,并且又导致细胞迁移性能改变,DNA损伤和基因组不稳定性的增加,并且受损的核电机组。因此,在过去的几十年里,细胞核的力学生物学在过去的几十年里越来越高。核生物力学的研究主要利用探针和/或光学显微镜来量化核的力学性能及其对物理扰动的反应。在本论文的上半年,我描述了两种研究核动力学的新方法。首先是侧视图,光纸荧光显微镜与原子力显微镜(AFM-LS)相结合,其能够与AFM连接的时间相关的多色3D光片成像。第二种方法是被称为尖端式的光瓣显微镜和荧光恢复的独特组合,其被称为尖端式溢出,我用于在整个2D图像上同时量化扩散。 In the latter half of this thesis, I describe how I have used both AFM-LS and SPIM-FRAP to study nuclear mechanobiology. SPIM-FRAP is used to show how intranuclear diffusion of NLS-GFP is slowed in nucleoli, but overall uncorrelated with chromatin structure on the length scale of single fluorophores. Additionally, I use SPIM-FRAP to show that sites of DNA damage are more stable than the surrounding diffuse repair proteins. AFM-LS is used to separate of the roles of chromatin and lamin A/C in nuclear compression, regarding both the mechanical response of the nucleus as well as local nuclear curvature. I also use multi-channel, 3D AFM-LS to show how compression alone via AFM, independent of nuclear rupture, is sufficient to induce DNA damage in nuclei. This indicates a novel mechanism by which nuclei incur double-stand DNA breaks. Finally, I provide the first review of mechanical models of nuclei, along with the development of a continuum mechanical model for AFM indentation. Together, these developments in methodologies along with the coupled insights into intranuclear dynamics, nuclear mechanics, and DNA damage improve both our means of studying and our current understanding of nuclear mechanobiology.

防御将通过缩放远程攻击:https://hhmi.zoom.us/my/hobsonchad

细节

日期:
3月17日
时间:
下午1时至3时