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Combining cutting edge molecular microbiology and super-resolution microscopy to reveal how bacteria divide

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  • Full or part time
    Dr S Holden
    Dr GJ Sharples
    Prof S J Foster
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

We are looking to recruit an outstanding student to work on uncovering the architecture of the Bacillus subtilis bacterial cell division septum by super-resolution microscopy.

Antimicrobial resistance (AMR) causes 700,000 deaths each year, predicted to rise to 10 million by 2050; new drugs are urgently required. A better understanding of the essential process of bacterial cell division will support identification of novel antibiotic inhibition strategies and targets. We recently discovered that the essential protein FtsZ guides synthesis of the mid cell cross-wall (septum) during bacterial cell division (Bisson Filho et al, Science 2017). However, it remains unclear how division proteins build a physically robust septum and how that structure is compromised during antibiotic treatment.

During this PhD you will establish high quality multicolour super-resolution microscopy of the Bacillus subtilis division septum using fluorescent D-amino acids, which label newly inserted cell wall material. You will use super-resolution microscopy to reveal how the bacterial cell division septum is built at nanoscale resolution, and how antimicrobials physically compromise septum integrity.

What will you be doing for your PhD research?
You will join an exciting multidisciplinary project team as the molecular microbiology and probe/ labelling development PhD lead, with responsibility for:
1) biological application of super-resolution imaging to understand how the bacterial cell division septum is built (molecular microbiology, bacterial genetics, biochemistry).
2) establishing a multicolour super-resolution microscopy protocol for imaging of the bacterial division site (immunostaining/ labelling, fluorophore photophysics, advanced microscopy)

You will join the Holden lab at Newcastle University (https://blogs.ncl.ac.uk/seamusholden/). We are an interdisciplinary lab that spans microbiology and biophysics, with group members from both disciplines. We are located at the Centre for Bacterial Cell Biology, Newcastle University, a world leading centre for molecular microbiology research. This work will be performed in collaboration with the Simon Foster lab in Sheffield, and the Gary Sharples lab in Durham.

What training will you receive?
You will specialize in two core fields: bacterial cell envelope microbiology and super-resolution microscopy. You will gain extensive practical experience of molecular microbiology, biochemistry, bacterial genetics, super-resolution microscopy, fluorophore photophysics, and quantitative data analysis.

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, eg. microbiology, molecular biology, biochemistry, biophysics.

For informal enquiries, please contact Dr Seamus Holden ([Email Address Removed]) with CV.

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as 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.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.



Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.

References

Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science, 355, 739-743 (2017).

Super-resolution fight club: A broad assessment of 2D & 3D single-molecule localization microscopy software, Nature Methods, 16, 387–395 (2019)

Movement Dynamics of Divisome and Penicillin-Binding Proteins (PBPs) in Cells of Streptococcus pneumoniae, Proc. Natl. Acad. Sciences USA, 111, 4566-4571 (2018)

Glycosylated nanoparticles as efficient antimicrobial delivery agents. Biomacromolecules 17: 2672-2679 (2016)

Exploring the links between peptoid antibacterial activity and toxicity. Med. Chem. Comm. 8: 886-896 (2017)

Human skin commensals augment Staphylococcus aureus pathogenesis. Nature Microbiology (2018) doi: 10.1038/s41564-018-0198-3

Molecular coordination of Staphylococcus aureus cell division eLife (2018) doi: 10.7554/eLife.32057

Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by Peptidoglycan Hydrolases mBio (2015) doi: 10.1128/mBio.00660-15

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