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High resolution electron microscopy of biological systems

Dowle, Miriam (2014)
Ph.D. thesis, University of Birmingham.

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This thesis demonstrates the relevance of advanced transmission electron microscopy (TEM) techniques such as aberration corrected scanning transmission electron microscopy (STEM) to the study of biological samples. By developing the application of these techniques to biologically relevant systems, this study shows how advanced EM can be an effective tool by providing insight into the structure of biological systems at the highest (i.e. atomic) resolutions. High angle annular dark field (HAADF) STEM has been used to gain insight into the core structure and iron loading mechanisms of the iron storage protein, ferritin. The iron content of ferritin was quantified using size-selected gold clusters as a mass balance, the first application of this technique to a biological sample. Preliminary structural studies of a novel colorectal cancer therapy have been undertaken, where polymeric alginate molecules chelate chemotoxic luminal iron in the colon. In particular the nano-structures built when alginates bind iron under physiological conditions have been established and investigated for the first time, using HAADF-STEM. Finally using TEM, it has been revealed for the first time the structures formed, and morphology changes induced, when proteins are encapsulated by membrane mimicking nano-discs.

Type of Work:Ph.D. thesis.
Supervisor(s):Palmer, Richard E. and Overduin, Michael and Chidgey, Martyn and Johnston, Roy
School/Faculty:Colleges (2008 onwards) > College of Engineering & Physical Sciences
Department:Department of Chemistry
Subjects:QH301 Biology
R Medicine (General)
Institution:University of Birmingham
ID Code:5235
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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