Material Immune Systems

PhD Project Summary

The vaginal microbiota plays a key role in women’s health. Low diversity microbiota dominated by Lactobacillus crispatus is considered as the hallmark of health. Conversely, a high diversity microbiota, leading to inflammation, is associated with adverse women’s reproductive health outcomes such as bacterial vaginosis, increased susceptibility to sexually transmitted infections and adverse pregnancy outcomes such as infertility and preterm birth. Inflammation is a key driver of women’s health and disease. We have identified a subset of anti-inflammatory lectins, innate immune receptors specialised in detecting glycan motifs, interacting specifically with the commensal bacterium L.crispatus. However, the consequences of these interactions remain unknown.

The aim of this project is to identify the bacterial ligands of these anti-inflammatory receptors, characterise the immune response triggered and develop chemical mimetics with improved anti-inflammatory properties.

The results of these project will not only help to better understand how the beneficial vs detrimental bacteria modulate the maternal immune system, but will also open new ways to develop synthetic glyco-molecules, mimicking the anti-inflammatory effect of the lactobacilli to prevent a broad range of women’s health diseases.

Methodology

The immunomodulatory glycans will be purified from Lactobacillus crispatus according to protocols established in the host laboratory. Briefly, L. crispatus will be grown and the glycans will be extracted and purified by size exclusion and affinity chromatography. The isolated glycans will then be analysed for binding to plant lectins as a proxy to determine glycan composition and by mass spectrometry.

The glycans identified as ligands of will then be tested for their ability to activate HEK reporter cell lines and monocyte derived dendritic cells. Signalling will be assessed by ELISA, Western Blot, flow cytometry and microscopy.

Finally, the bacterial glycans will be coupled to multivalent scaffolds and their biological activity will be assessed.

PhD Supervisor: Alexiane DecoutLink opens in a new window

Entry Requirements

This PhD studentship is available for Home students only.

Applicants must hold a Master's degree with some experience in immunology, host pathogen interactions or glycobiology. Experience in chemistry or biochemistry would also be useful but is not essential.

Funding

Student tuition fees are covered for the four-year project. A stipend will also be provided for the first three years.

How to apply

As part of your application you will need to supply academic references, a supporting statement and evidence of your academic qualifications.

To apply for this PhD project, please complete the research course application form, selecting MPhil/PhD in Medical Sciences as the course option.

Deadline for applications is Friday 30 August 2024.