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Developing an open source, low cost, high performance super-resolution microscope for bacteriology and antimicrobial drug discovery

Primary Supervisor: Dr Seamus Holden, University of Warwick

Secondary supervisor: Professor Christopher Dowson, University of Warwick

PhD project title: Developing an open source, low cost, high performance super-resolution microscope for bacteriology and antimicrobial drug discovery

University of Registration: University of Warwick

Project outline:

BACKGROUND

Bacterial cells are tiny but highly spatially organized. Light microscopes are essential to understanding how bacteria grow and divide, and in helping to develop new antibiotic drugs to combat the growing threat of antimicrobial resistance.

Because bacteria are so small – about 1 μm in size – high resolution fluorescence microscopes are required for cutting edge bacteriology research. Super-resolution microscopes which break the 250 nm diffraction barrier of light to reach a resolution of 100 nm or better are even better, but these microscopes usually cost several hundred thousand pounds, making them a scarce resource shared between multiple labs at well-funded institutions, and usually inaccessible in resource limited settings.

WHAT WILL YOU BE DOING FOR YOUR PHD RESEARCH?

During this PhD project you will address this problem by designing, building and testing a super-resolution fluorescence microscope for cutting edge bacteriology that costs just a few thousand pounds, a fraction of the cost of traditional microscopes, and is easily accessible to most laboratories.

This will be possible because 1) recent developments in open source hardware such as 3D printing and cheap, powerful cameras dramatically lower the cost of designing and building microscopes and 2) much of the cost of traditional high-end microscopes goes towards features which are not necessary for thin bacterial samples, such as large depth range or interchangeable microscope lenses.

By focussing exclusively on the feature set required for bacteriology, and adapting low cost hardware and fabrication approaches from the maker movement (eg Arduino controllers, 3D printing) and the machine vision industry, you will create a disruptive technology that dramatically reduces the price and increases the accessibility of cutting edge bacterial microscopy.

The project will use optics, CAD design, engineering, image processing, and super-resolution microscopy. The project will also involve imaging live bacterial samples, in which you will receive full training and in which no prior experience is required.

All technology developed will be released open source, including software and hardware designs, to maximize broad access and uptake. There is also the potential for the student to be involved in follow-on commercialization activities.

You will join the Holden lab at Warwick University. We are an interdisciplinary lab that works across the disciplines of advanced microscopy, biophysics and bacteriology. We study basic principles of biological spatial organization in living cells, with a particular focus on how bacteria divide and grow [1,2]. To achieve this we develop novel experimental methods based on single molecule & super-resolution microscopy, microfabrication and microfluidics [2–4].

IS THIS PROJECT RIGHT FOR YOU?

This PhD project would suit candidates with a first degree in the physical, engineering or computing sciences with an interest in working across disciplines, or candidates with a first degree in the biological sciences and demonstrable experience in optics (eg research experience or MRes specialisation).

You will receive world class training in advanced microscopy, microscopy, image data science and bacterial cell biology. Prior experience in bacteriology is not required.

In the Holden lab we welcome and celebrate diversity in all its forms. We particularly encourage applications from women and BAME individuals, as both of these groups are systematically underrepresented within the physical sciences.

References:

  1. A.W. Bisson-Filho et al., Science 355 (2017) 739–743.
  2. K.D. Whitley et al., Nat. Commun. 12 (2021) 2448.
  3. K. Whitley et al., Preprints (2021).
  4. S.J. Holden et al., Proc. Natl. Acad. Sci. 111 (2014) 4566–4571.

BBSRC Strategic Research Priority: Sustainable Agriculture and Food:Microbial Food Safety & Renewable Resources and Clean Growth: Industrial Biotechnology & Understanding the Rules of Life: Microbiology & Systems Biology & Integrated Understanding of Health: Ageing

    Techniques that will be undertaken during the project:

    • Advanced light microscopy, super-resolution fluorescence microscopy (supervision training)
    • Optics, optical design, microscope design and microscope development (supervision training)
    • Open source engineering including CAD design, 3D printing/ rapid prototyping, electronics, control software development (supervision training)
    • Image data science, quantitative image and data analysis with Python and ImageJ (supervision training).
    • Bacterial cell biology, bacterial cell culture (supervision training)

    Contact: Dr Séamus Holden, University of Warwick