Sheep adult stem cells can be used in the lab to grow 3D gastrointestinal (GI) structures called GI organoids. In our lab we have developed sheep ‘mini-gut’ GI organoids that allow the study of interactions between the host and parasitic gastrointestinal nematodes (GINs).
In temperate regions the brown stomach worm Teladorsagia circumcincta is the principal GIN of sheep. This parasite develops in the abomasum (which is analogous to the gastric stomach) causing significant mucosal damage associated with host inflammatory immune responses. To establish infection T. circumcincta secretes excretory/secretory (ES) products that it uses to modulate the immune response and cellular physiology of the host. There is emerging evidence that extracellular vesicles (EVs), a subcomponent of ES, play an important role in host/parasite interaction.
The overall aim of this project is to use ovine abomasum organoids to identify and characterise active components of T. circumcincta EVs and to study their impacts on host physiology. The specific objectives of the project are as follows:
- Objective 1. Characterise host transcriptome response to T. circumcincta EVs. This objective will use RNA-sequencing (RNA-seq) to characterise the transcriptomic response of ovine abomasum organoids to T. circumcincta EVs.
- Objective 2. Identify active components of T. circumcincta EVs. This objective will use proteomic techniques to identify components of T. circumcincta EVs using ovine abomasum organoids to screen for bioactive components.
- Objective 3. Validate the impact of defined EVs components on host physiology. Using cell imaging and transcriptomic techniques this objective will characterise the impacts of defined EV components on the host tissue.
The PhD candidate will work closely with the organoid research team at MRI and receive training in cutting edge methodologies, including: 3D organoid cell culture; in vitro experimental infection models with parasitic nematodes; 3D immunofluorescent imaging; RNA-sequencing (RNA-seq), proteomic analysis and bioinformatics training.
Application Process:
To apply for an EASTBIO PhD studentship How to apply | eastbio (eastscotbiodtp.ac.uk) follow the instructions below:
After you have discussed the projects of interest to you with the project supervisors, download and complete our Equality, Diversity and Inclusion survey EASTBIO DTP Equality, Diversity & Inclusion Form 2022 (online surveys.ac.uk) and then download and complete the EASTBIO Application Form and submit the application form plus your academic transcripts to Moredun Research Institute Human Resources at [Email Address Removed]
Download and send the EASTBIO Reference Form to your two academic/professional referees, and ask them to submit these directly to [Email Address Removed] (Link to the form can be found here: How to apply | eastbio (eastscotbiodtp.ac.uk) by 16th December 2021.
If you are nominated by the supervisor(s) of the EASTBIO PhD project you wish to apply for, they will provide a Supervisor Support Statement.
Unfortunately, due to workload constraints, we cannot consider incomplete applications.
We can only accept applications from individuals who have the right to work in the UK.
All EASTBIO (online) interviews will be in the week 7-11 February 2022 with awards made the following week
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