Bacterial genes to function: Determining the roles of the gut microbiome in preterm infant health and disease

Preterm infants born <32 weeks gestation are 'immature' physiologically, anatomically and immunologically. Around 10% will develop necrotising enterocolitis (NEC), a deadly inflammatory mediated bowel disease. Abnormal gut microbiome development is integral to NEC pathogenesis. Metagenomic and 16S amplicon sequencing approaches have shown that NEC infants have reduced gut microbial diversity, increased Proteobacteria (gram-negative), and reduced Bifidobacterium (gram-positive).

However, these approaches alone do not allow for the functional roles of bacterial species within the microbiome to be characterised. In depth study of these functions and how different species interact is critical to understanding the microbe-microbe and microbe-host interactions that drive and maintain changes in the gut microbiota of NEC or healthy infants.

The project will be based on preterm infant health and disease, but there is flexibility in what the student can focus on, which can be modified as the project progresses. Some key objectives are likely to include:

1) Determine the metabolic functional capacities of bacterial strains isolated from both healthy and NEC infants

2) Investigate metabolic cross-feeding between bacterial strains and determine competition or synergism

3) Experimentally test the function of bacterial strain interactions within the host intestinal epithelium using a powerful ex vivo preterm organoid co-culture model

The student will work closely with academic and clinical supervisors and will have access to the Great North Neonatal Biobank, the largest biobank of preterm samples anywhere in the world. From this resource we have already isolated ~250 novel bacterial and fungal isolates (currently undergoing whole genome sequencing).

Our group have also established a novel method for generating preterm organoids and performing co-culture of anaerobic bacteria and preterm epithelium. This PhD studentship will advance our existing research portfolio and build on the tools and extensive data we have already generated. This promises to give a deep understanding of preterm health and disease with potential for developing new biomarkers and therapeutics.

The clinically focused work incorporates both discovery and translational aspects. During the course of this interdisciplinary project, the student will gain a wide range of relevant experience in wet-lab techniques including microbiology, molecular biology, biochemistry, tissue culture, transcriptomics (host), metatranscriptomics (bacteria), alongside computational skills including the bioinformatic and statistical analysis of large multi-omic datasets. Such skills are highly-transferable.
We are a diverse, fun, and inclusive research group, with positive research culture at the heart of our ethos. We encourage applications from under-represented groups and first-generation students.