Nutrition of the Respiratory Microbiome

Secondary Supervisor(s): Dr Lucy Crouch

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Microbiology)

Project Outline

The lower respiratory tract has a microbiome. It is sparser than the gut microbiome and much less well characterised, but similarly varies in health and disease, has stable composition and has direct interactions with the immune system. In this project we aim to discover how this microbiome functions and particularly how it obtains nutrition focusing on respiratory mucin as carbon source and the nutritional links between different members in this ecosystem.

The project aims are to

• Characterise the mucin degrading and binding capabilities of the Respiratory Microbiome Group culture collection.
• Build a model consortium that represents the healthy respiratory tract using high throughput screening of artificial communities.
• Subject this model to challenges such as pathogen invasion, drug interactions and nutrient availability.

This will allow us to build a picture of how the respiratory microbiome functions in health, identify how it responds to changes in its environment and how to predict these responses. It will also allow us to identify keystone species that are central to the function of this ecosystem and start to give us the tools to alter the respiratory microbiome to promote health.

The work is a collaboration between the Respiratory Microbiome Group (Cox) and the Crouch Group, bringing together expertise in microbial ecology and in glycobiology at the interface of the host and microbiome. The PGR will benefit from working across both groups who are co-located in the same lab space.

Understanding the impact of the innate respiratory resistome on AMR

Secondary Supervisor(s): Dr Michelle Buckner

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Microbiology)

Project Outline

Respiratory infections drive the global AMR crisis. Most adult prescriptions of antibiotics are for respiratory infections, the majority of which are empirical prescriptions without diagnosis of an infectious agent and have systemic impacts on the human microbiome. The respiratory microbiome is understudied, but is present in all people, it is separated into the upper and lower respiratory tracts and contains many organisms, however the level and type of innate antimicrobial resistance to various classes of clinically used antibiotics remains unknown.

This project aims to characterise the extent of antimicrobial resistance, whether and how it transfers between organisms in the respiratory microbiome and whether the combination of organisms present gives synergistic resistance to antimicrobial challenges.

In this studentship the postgraduate researcher will:

• Define the respiratory resistome using the extensive Respiratory Microbiome Group (Cox) respiratory microbiome culture collection.
• Demonstrate the extent of AMR mobility within and between species.
• Identify how co-culture of respiratory consortia might enhance or reduce antimicrobial susceptibility.

Overall we aim to understand the fundamentals of resistance in the respiratory microbiome in healthy individuals to allow more targeted development of antibiotics or reveal alternative approaches to increase the efficacy of treatments.

This project is a collaboration between the Buckner group and the Respiratory Microbiome Group and the PGR will benefit from the support of both, developing a unique combination of skills in AMR research and microbiome research.

Defining interactions between vaccine targetable airway pathobionts

Secondary Supervisor(s): Dr David Cleary

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Microbiology)

Project Outline

The upper and lower respiratory tract harbours a microbiome that includes potential pathogens that can become disease causing when the immune homeostasis is challenged. Diverse species of Haemophilus, Neisseria are always present in the respiratory tract and often at the same time. Most understanding of these important potential pathogens comes from studying them in disease and in isolation, but most of the time these organisms are apparently harmless and also never present alone.

In this project we aim to

• Develop innovative methods to examine pathobiont interactions in physiologically relevant models including mixed-species biofilms, OnChip micro-communities and in co-culture with host epithelial cells.
• Investigate pathobiont-pathobiont, and host-pathobiont interactions using transcriptomic and mass spec approaches
• Refine interaction models between key pathobionts in the context of known species heterogeneity using the extensive isolate collections of the Cox and Cleary groups

Overall we aim to resolve the function and interaction of these understudied ubiquitous pathobionts.