Uncovering the mediators of colonization resistance to pathogens facilitated by the gut microbiome

• Funding – self-funded/externally sponsored applicants   (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

Colonization resistance refers to the ability of the microbiome in an organ to prevent colonization of that organ by pathogenic microorganisms [1]. For example, the gut microbiome of mice protect them from infection by the intestinal pathogen Salmonella typhimurium.  Loss of gut microbiota, by antibiotic treatment for example, can lead to susceptibility to infection. Despite some evidence for active antagonism against invading pathogens, mechanisms underlying colonization resistance are poorly understood. Understanding this phenomena could lead to ways to prevent and treat infection with microbes with anti microbial resistance (AMR).  

    We propose to use Caenorhabditis elegans, a roundworm with a robust innate immune system, to identify microbiota species mediating colonization resistance to human microbial pathogens. The C. elegans gut, colonized first with individual or a consortia of gut microbiota derived (i) from C. elegans or (ii) from mice will be subsequently infected with pathogenic bacteria [2-4]. We will assess the contribution of the entire microbiota and individual species on colonization by flurescently labelled pathogens. Subsequently, we will use proteomics, liquid chromatography mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) approaches to identify soluble mediators of active antagonism and inhibitory metabolites. We will use worms lacking innate immune mechanisms to understand the effect of host genetics on colonization resistance offered by the gut microbiome [5].  C. elegans provides a genetically and optically tractable model to study colonization in a short amount of time.  

      The PhD student will acquire training in C. elegans maintenance, microbiome colonization and infection. The student will also receive training in LC-MS and GC-MS analyses of individual bacterium and complex, multi-species samples.  The student will be provided additional training in scientific writing, statistical analyses and data management at University of Dundee in addition to mentoring support throughout and during career transition.   

REFERENCE: 

1. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat Rev Microbiol. 2023 Jun;21(6):347-360. doi: 10.1038/s41579-022-00833-7. PMID: 36539611. 

2. CeMbio - The Caenorhabditis elegans Microbiome Resource. G3 (Bethesda). 2020 Sep 2;10(9):3025-3039. doi: 10.1534/g3.120.401309. PMID: 32669368. 

3. Olfactory basis for essential amino acid perception during foraging in Caenorhabditis eleganseLife13:RP101936https://doi.org/10.7554/eLife.101936.1 

4. Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community. Nat Commun. 2023 Aug 8;14(1):4780. doi: 10.1038/s41467-023-40372-0. PMID: 37553336. 

5. Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science. 2011 May 6;332(6030):729-32. doi: 10.1126/science.1203411. Epub 2011 Apr 7. PMID: 21474712. 

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.