Development of a relevant cocultured cell skins models to understand the development of biofilms in wounds

About the Project

Bacteria colonize skin but in general, do not form biofilms when the skin is intact; however, bacteria do form biofilms in wounds which delays healing. The presence of biofilms can reduce the effectiveness of antibacterial treatments, and the skin and wound environments, and microbiota crosstalk which in turn may influence the composition of biofilms. Biofilms, heterogenous bacterial communities adhering to a surface, are surrounded by a complex matrix composed of exopolysaccharides, proteins, and extracellular DNA. This structure not only upholds the rigid architecture, but additionally protects from physiological and chemical stresses such as evasion of the hosts immune system and shear forces. The components of the biofilms exhibit viscoelastic properties meaning they can display both fluid and elastic rheological characteristics, which are important to understand factors affecting the penetration of drugs in biofilms.

So far, studies of biofilms in wounds have typically relied on in vivo animal systems or simple 2D in vitro models; thus reliable in vitro models to study biofilms are lacking; their development would be in line with the 3Rs (replacement, reduction and refinement) principle of in vivo research. Here we propose to developing in vitro models based on keratinocytes and dermal fibroblasts cultured on supported membranes and assess the development and resistance to treatment of biofilms within novel in vitro models.

Key objectives:

• To develop coculture of keratinocytes and dermal fibroblasts on transwell to understand the formation of tight cell cultures and then develop coculture of keratinocytes and dermal fibroblasts on Ibidi µ-Slide Membrane ibiPore Flow chambers,
• To define appropriate conditions for the formation of biofilms of specific bacteria.
• To characterise the biofilm structural and antimicrobial tolerance properties using methods that include microrheology, fluorescence and confocal microscopy.
• To assess changes in the biofilm structural properties following treatment.

Eligibility

Applicants are expected to hold, or about to obtain, a minimum upper second-class undergraduate degree (or equivalent) in microbiology, (bio)chemical engineering, chemistry, biochemistry, biophysics, pharmaceutical sciences or related subject. A Master’s degree in a relevant subject and/or experience in microbiology. (bio)chemical engineering, chemistry, biochemistry, biophysics or related subject is desirable but not necessary. They are also expected to have a strong will to learn different scientific aspects.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Pharmaceutical Science Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 (med) fee. Details of our different fee bands can be found on our website View Website

References

Buzza et al. (2023) Microbiology Spectrum DOI: 10.1128/spectrum.02527-22
HC Flemming et al., Nat Rev Microbiol (2023), DOI: 10.1038/s41579-022-00791-0
Hoffman et al., Biomedicines (2023) DOI : 10.3390/biomedicines11041056
Chen et al. Nature (2018) DOI:10.1038/nature25177