University of Warwick PhD Opportunities

Microbial community assembly in early-stage cystic fibrosis lung infection

Secondary Supervisor(s): Dr Saskia Bakker, Dr Alexiane Decout

BBSRC Research Themes:

• Understanding the Rules of Life (Microbiology)

Project Outline

For decades, people with the genetic condition cystic fibrosis have faced a predictable pattern of lung infection and declining health. Excessive lung mucus promotes first colonisation of the lungs by commensal bacteria from the host’s nose and throat, then invasion of this microbiome by a sequence of pathogens that progressively reduce lung function and culminates in a lung community dominated by one pathogen species (usually Pseudomonas aeruginosa). The availability of CFTR modulators, which correct the underlying genetic mutation at the protein level, has changed this course of infection and drastically improved the health of people with CF. But modulators are not a complete cure, and we need to understand the new ecology of CF lung communities to further improve health.

In this project, you will establish a modified version of our established ex vivo pig lung model that better represents the lung environment when CFTR modulators are prescribed. The model uses lungs from pigs killed for meat, and synthetic CF mucus. You will culture lab and environmental isolates of pathogens (Pseudomonas aeruginosa, Staphylococcus aureus and Non-typeable Haemophilus influenzae) in the modified model, in the presence and absence of a community of oropharyngeal bacteria. You will assess the growth habit (single cells, aggregates or biofilm?), community structure (well-mixed or spatially segregated?), antibiotic tolerance and virulence of single-species and polymicrobial infections, and assess how well different pathogens can invade your early-stage lung disease model, compared with our established late-stage chronic infection model. You will develop one hypothesis that can be tested using an -omics approach (transcriptomics, whole-genome sequencing, metabolomics or proteomics).

The project combines fundamental microbiology, microbial ecology and advanced microscopy. Depending on your interests and on project progress, the amount of focus given to each area is flexible.

Microbial community assembly and dynamics in endotracheal tube biofilms

Secondary Supervisor(s): Dr Saskia Bakker, Professor Jeremy Webb

University of Registration: University of Warwick

BBSRC Research Themes:

• Understanding the Rules of Life (Microbiology)

Project Outline

Bacteria and some fungi predominantly grow as biofilms: multicellular aggregates encased in self-produced polymers that protect from immune and antibiotic attack. The endotracheal tubes (ETTs) used to connect hospital patients to ventilators quickly become colonised by biofilms of microbes from the patient’s mouth, nose and skin, and from the environment. Fragments of this biofilm can detach and disperse to the lungs, leading to ventilator-associated pneumonia (VAP). Treating & preventing ETT biofilm is a major unmet healthcare need – there are no effective biofilm-resistant ETTs in clinical use, and antimicrobial treatment fails in around 50% of patients. It is hard to predict which antimicrobials might work because the unique in vivo environment alters microbial physiology, and antimicrobial sensitivity. In this project, you will explore how these antimicrobial-tolerant biofilm communities assemble and persist in a model of ETT biofilm.

Our lab developed a way to grow multispecies communities of bacteria and fungi on ETTS in the lab, using growth medium that we developed to chemically mimic the mucus in patient airways. We can either grow these communities on sections of ETT in synthetic mucus in a culture plate, or we can use a bespoke robotic ventilator to grow the communities on the ETT under realistic fluid and air flow. You will use this model to characterise the ecological succession of ETT communities from pioneer colonisers to a climax community, and you will explore what changes in microbial physiology and/or gene expression underly high levels of antimicrobial tolerance. This work will allow you to test some new ways of preventing biofilm attachment to the tube, or of enhancing antimicrobial efficacy.

The project combines fundamental microbiology with microbial ecology, advanced microscopy and chemistry. Depending on your interests and on project progress, the amount of focus given to each area is flexible.

Apply

For full information and to apply, please visit the University of Warwick website.