PhD studentship


Fully funded PhD studentship


Title: Role of the stringent response to promote biocide induced antibiotic tolerance in Staphylococcus aureus biofilms.

Supervisors: Prof Kim Hardie (School of Life Sciences, University of Nottingham), Prof Dr. Christiane Wolz (University of Tübingen), Prof Jonathon Aylott (School of Pharmacy, University of Nottingham), Prof. Dr. Hannes Link (University of Tübingen)

Project Overview:

The selection of antibiotic tolerant bacteria is of emerging concern and is thought to contribute to treatment failure. Our preliminary data supports the hypothesis that widely used biocides can promote such tolerance in the major human pathogen Staphylococcus aureus by activation of the stringent response. This was also observed in biofilm grown bacteria. The stringent response regulated phenol soluble modulins (PSMs) are likely involved in biocide induced biofilm composition. The studentship will build on our previous cooperation and benefit from complementary global gene expression data, methods and expertise. Transcriptome and metabolome data will be generated to decipher the molecular mechanisms triggered by biocide induced stringent response and biofilm alterations. This will inform future treatment options. In Tubingen, the student will define underlying molecular pathways by construction and global analyses of a defined set of engineered strains. In Nottingham, the student will analyse biofilms with a special focus on the role of PSMs in polymicrobial biofilms and antibiotic tolerance. Working across disciplines, the student will undertake cross-correlative imaging to map gene expression, microbial metabolism, and biofilm architecture with PSM production and biocide exposure. Including our novel oxygen-sensitive nanosensors within biofilms will enable parallel dynamic monitoring of reactive oxygen species.

The two universities provide first class facilities and learning environments supported by expertise and dedicated researchers. The collaboration enables the Tubingen tools (mutants) to be analysed on UoN imaging platforms using their range of biofilm models.

The supervisors have vibrant research groups hosted in state-of-the-art laboratories. Kim Hardie has an extensive track record in molecular microbiology of pathogenicity and leads the pathogen imaging facility within the Cross-disciplinary Biodiscovery Institute. Jon Aylott has developed optical nanosensors for sensitive real time monitoring of pH and oxygen. Jon and Kim collaborate to map the environmental microniches of biofilms, and are co-Investigators of the National Biofilm Innovation Centre (NBIC). At the University of Tübingen, Christiane Wolz is a leading expert in the study of the stringent response, and has a broad selection of defined mutants supported by expertise in molecular engineering. Hannes Link leads a metabolomics pipeline that generates population measurements to complement the 2D and 3D mapping of metabolites using a range of analytical tools housed within the flagship nmRC facility at the University of Nottingham.

The training opportunities include cutting-edge fluorescent microscopy, transcriptomics, optical nanosensor utilization, LC-MS metabolomics, cryo-EM, cryo-orbiSIMS, and molecular microbiology. In addition both Universities offer a host of practical training courses, there is an active research seminar programme and wellbeing support.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers

Eligibility:

  • Applicants should hold or expect to gain a first degree in microbiology or a related relevant area and have obtained at least a 2.1 degree.

Funding Details:

  • Starts July 2022

  • 3 year award, FT

  • Funding covers full tuition fees plus stipend of £15,609 rising with inflation annually for UK Students, EU Students and International Students

  • Based in UK, with 12 months in Germany

How to apply:

Please send CV and cover letter to Edward Gordon (brzedg@exmail.nottingham.ac.uk).

Application Deadline: 30th May 2022

Further Enquiries:

Please note that, where a candidate is successful in being awarded funding, this will be confirmed via a formal studentship award letter; this will be provided separately from any Offer of Admission and will be subject to standard checks for eligibility and other criteria.

For further details please contact kim.hardie@nottingham.ac.uk or Christiane.Wolz@uni-tuebingen.de

References:

1. Brauner et al., Nat Rev Microbiol, 2016. 14:320. DOI: 10.1038/nrmicro.2016.34

2. Kuehl et al., J Antimicrob Chemother, 2020. 75:1071 DOI: 10.1093/jac/dkz559

3. Westfall et al., Antimicrob Agents Chemother, 2019. 63:e02312. https://doi.org/10.1128/AAC.02312-18

4. Yan & Bassler. Cell Host Microbe, 2019. 26:15 DOI: 10.1016/j.chom.2019.06.002

5. Fritsch et al., Free Radic Biol Med. 2020. 161:351. https://dx.doi.org/10.1016/j.freeradbiomed.2020.10.322

6. Horvatek, et al., PLoS Genet, 2020. 16:e1009282. https://doi.org/10.1371/journal.pgen.1009282

7. Hollmann et al NPJ Biofilms and Microbiomes. 7, 50 (2021). https://doi.org/10.1038/s41522-021-00221-8

8. Zhang et al Analytical Chemistry 92:9008 https://doi.org/10.1021/acs.analchem.0c01125