Development of novel super-resolution and volume imaging techniques for visualising cellular function and ultrastructure in biomedical applications

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Euchner, Jonas Philipp ORCID: https://orcid.org/0009-0007-4678-1841 (2024). Development of novel super-resolution and volume imaging techniques for visualising cellular function and ultrastructure in biomedical applications. University of Birmingham. Ph.D.

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Abstract

Fluorescence and electron microscopy are at the forefront of resolving the complex intracellular dynamics at the cellular nanoscale, a task that continues to push the limits of biomedical research.
Within this thesis significant advancements in cellular nanoscale imaging are achieved through the development of novel super-resolution and volumetric imaging techniques. Central to this work is the custom-built super-resolution microscope, which underpins the methodological advancements elaborated in the subsequent chapters. These developments tackle key challenges in microscopy, including determining the degree of labelling for protein-tags, preserving fluorophores in acrylic resins for correlative light-electron microscopy (CLEM) and implementing novel super-resolution microscopy techniques in a cellular context.
Furthermore, the thesis demonstrates the utilisation of advanced super-resolution techniques in various biomedical applications. It unravels the structural changes of liver sinusoidal endothelial cells in a senescent microenvironment, shedding light on the underlying response mechanisms correlated to hepatocellular cancer.
Last but not least, a major focus within the thesis is put on the refinement and application of in-resin super-resolution microscopy as well as volumetric CLEM, facilitated by novel resin compositions. These compositions quantitatively preserve fluorophores during embedding, promising markedly improved imaging fidelity in super-resolution and volumetric CLEM. The findings within this thesis will have widespread implications in future research in resolving the functional organisation within the cellular ultrastructure.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):