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Developing new tools to understand bacterial cell wall biophysics using single molecule microscopy, deep learning and quantitative modelling


Biosciences Institute

Dr S Holden , Dr GJ Sharples , Prof Ricardo Henriques Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Bioinformatics Biophysics Microbiology Molecular Biology

About the Project

We are looking to recruit an outstanding physicist or computer scientist to develop new hardware-software microscopy tools for single molecule imaging inside live bacteria. 

We seek to understand how nanoscale proteins build a precisely shaped microscale bacterial cell envelope. To achieve this, we use single molecule tracking microscopy to watch individual protein molecules directly inside living cells as they remodel the cell wall. Imaging tiny proteins inside living cells is an intense technical challenge, requiring sophisticated image data science and biophysical analysis methods to translate single molecule trajectories into quantitative models of how proteins work as biological nanomachines. 

WHAT WILL YOU BE DOING FOR YOUR PHD RESEARCH? 

During this PhD you will develop a fully automated, open source, high throughput hardware-software method for single molecule tracking of individual proteins in live bacteria. This broadly accessible tool will be useful to many biophysicists and bacteriologists across the world. Alongside this, you will develop a computational model of cell wall protein dynamics, to quantitatively test models of cell wall remodelling by comparison to observed single molecule data. 

You will join the Holden lab at Newcastle University (https://blogs.ncl.ac.uk/seamusholden/). We are an interdisciplinary lab that works across biophysics, advanced microscopy and bacteriology. We are located at the Centre for Bacterial Cell Biology, Newcastle University, a world leading centre for bacteriology research. This work will be performed in collaboration with computational and optical biophysics experts at the Ricardo Henriques lab in IGC Portugal (https://henriqueslab.github.io/), and molecular microbiology experts at the Gary Sharples lab in Durham University. Collaborative visits and knowledge exchange with both labs are planned during the PhD. 

In the longer term this work will help fight antimicrobial resistance by contributing to understanding how antibiotics stop bacterial growth and division. 

IS THIS PROJECT RIGHT FOR YOU? 

We are seeking a scientist with a good degree (BSc/MSci 2(1) or above, or MSc) in a relevant field, e.g. Physics, Computer Science.

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

For informal enquiries, please contact Dr Séamus Holden (). 

HOW TO APPLY 

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

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2. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science, 355, 739-743 (2017).
3. Super-resolution fight club: A broad assessment of 2D & 3D single-molecule localization microscopy software, Nature Methods, 16, 387–395 (2019).
4. A bacteriophage mimic of the bacterial nucleoid-associated protein Fis. Biochem J. 477: 1345-1362
5. On the antibacterial activity of azacarboxylate ligands: lowered metal ion affinities for some bis-amide derivatives of EDTA do not necessarily mean reduced activity. Chem. Eur. J., 2018, 24: 7137-7148.
6. Exploring the links between peptoid antibacterial activity and toxicity. Med. Chem. Comm., 2017, 8: 886-896
7. ZeroCostDL4Mic: an open platform to simplify access and use of Deep-Learning in Microscopy. bioRxiv (2020, https://doi.org/10.1101/2020.03.20.000133).
8. Fast live-cell conventional fluorophore nanoscopy with ImageJ through super-resolution radial fluctuations. Nature Communications, 7:1-9 (2016).
9. Content-aware image restoration: pushing the limits of fluorescence microscopy. Nature Methods, 15(12):1090-1097 (2018).
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