We are amid a global climate crisis, which requires drastic reductions in greenhouse gas (GHG) emissions. At the same time, there is an unprecedented demand for high quality, nutritious food to support the growing human population. Since ~49% of all agricultural GHG emissions come from ruminant livestock, as a by-product of bacterial fermentation in the rumen, targeting the UK’s 22.8 million sheep and 9.4 million cattle offers a unique opportunity to make game-changing strides towards meeting the UK’s net zero carbon target of 2050.
Infections caused by parasitic helminths are responsible for >55% of livestock diseases and are a major concern for producers worldwide. Whilst it is well-known that helminths secrete a range of molecules that modulate the host immune response to ensure their long-term survival and reproduction, we are just beginning to explore how helminths interact with, and influence, the host microbiome. Our recent work has shown the rumen fluke, Calicophoron daubneyi, may increase methane emission intensity in sheep. We hypothesize that rumen fluke influence the composition of the host rumen microbiome such that methanogenic species prevail. In support of this, we, and others, have shown that molecules secreted by rumen fluke show antimicrobial activity and can shape microbial communities in the rumen. In this project we will investigate how C. daubneyi influence the microbiome via direct antimicrobial action but also via modulation of host innate immune responses to rumen microbial signatures.
Using our unique -omics resources we have identified a several molecules, secreted by the parasite, with putative direct antimicrobial activity or the ability to modulate the response of innate immune cells to microbial-associated molecular patterns (MAMPs; e.g. lipopolysaccharide) displayed by rumen microbes. In this project we will investigate this host-parasite-microbiome axis to begin to uncover how parasite infection influences GHG emissions from livestock.
The project has 3 major aims:
1) Characterise antimicrobial/immunomodulatory molecules secreted by rumen fluke
Using a multi-omics approach we have identified several putative antimicrobial/immunomodulatory molecules in rumen fluke secretions, many of which exist as multi-member families. Here, we will exploit quantitative transcriptome datasets (for 4 developmental stages of C. daubneyi uniquely available in Dr Robinson’s lab) to characterise these families and rationally select individual molecules for further testing. Candidates with conserved domains required for antimicrobial/modulatory activity (and displaying expression profiles indicative of rumen-specific roles) will be produced as purified recombinants, using our standard protocols. Shorter peptides will be chemically synthesised.
2) Test the fluke molecules on the rumen microbiome using an in vitro fermentation model
We will add rumen fluke molecules (or live flukes) to rumen microbes using an in vitro fermentation model. The fluke molecules will be added at a range of concentrations and methane measurements will be taken over 24 hrs and samples will be taken for quantification of volatile fatty acids and pH. Bacterial, protozoal and methanogen densities will be determined using established qPCR protocols. Samples will also be subjected to metataxonomy analysis using primers that will amplify both bacteria and methanogens for Illumina MiSeq sequencing.
3) Establish a rumen epithelial cell model to investigate immunomodulation by C. daubneyi
Rumen bacteria are predominantly gram negative and bear microbe-associated molecular patterns (MAMPs) such as lipopolysaccharide on their surface. Detection of MAMPs by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) expressed by epithelial cells leads to inflammatory responses, the resolution of which will result in tolerance to commensal microbes or clearance of pathogens. We have identified a number of molecules secreted by C. daubneyi that have the capacity to alter how PRRs recognise and respond to rumen bacteria MAMPs. Here, we will establish a novel in vitro model, using a bovine epithelial cell line, to investigate the transcriptional and immunological response to rumen fluke secreted proteins.
We envisage that determining helminth-microbiome-host interactions will have broad implications for animal health and immunity, production efficiency and reduction of GHGs. This project provides an exciting opportunity to gain expertise in translational parasitology, immunology and microbiome research.
Specific skills/experience required: An undergraduate degree in the biosciences.
Start Date: 1 October 2023.
Duration: 3 years
How to apply: Applications must be submitted online via: https://dap.qub.ac.uk/portal/user/u_login.php
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