Nanoscopic methods to visualise antimicrobial attNanoscopic methods to visualise antimicrobial attackack

Lead Research Organisation: University College London
Department Name: London Centre for Nanotechnology

Abstract

The human immune system has a variety of tools available to combat infections including the degradation of bacterial cell walls by antimicrobial peptides or intricate pore-forming machinery such as the membrane attack complex. Since the bacterial cell wall consists of multiple layers, the mechanisms of such degradation are non-trivial to determine. In this project, the student will develop atomic force microscopy, fluorescence microscopy and nanobody labelling methods to visualise the action of antimicrobial agents in live bacteria in real time with high spatial resolution.

The application of these nanoscopic methods will be extended to a more detailed characterisation of antimicrobial action on composite membranes encasing bacterial cells, with application to pore forming proteins and antimicrobial peptides. Such characterisation will serve to gain a better understanding of how our body regulates its bacterial population and resist bacterial invasions, as well as to guide the design of next-generation antibiotics.

The project will be carried out in a highly interdisciplinary environment, interfacing between Prof Hoogenboom's group at the London Centre for Nanotechnology, UCL and Dr Ryadnov's group at the NPL. For the student, this project provides an excellent opportunity to gain a comprehensive experience in antimicrobial design, biophysics and biology and to advance a mechanistic understanding of antimicrobial processes together with the underlying physics of micro-/nanoscopy.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509577/1 01/10/2016 30/09/2021
1905095 Studentship EP/N509577/1 26/09/2017 30/09/2021 Georgina Benn
 
Description We have established a reliable protocol for imaging bacteria by AFM, which we may now use to answer questions surrounding this project. This work is published here: Analyst, 2019,144, 6944-6952.

Furthermore, with our collaborators, we have gained further insight into bacterial killing by the complement system (part of your immune systems defence against pathogens). A preprint of this work can be found here: https://doi.org/10.1101/2019.12.17.877639
Exploitation Route We, and others, may now use this work to gain high resolution structural information of bacterial surfaces.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology