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EASTBIO: Modelling host/parasitic nematode interactions with ovine ‘mini-gut’ organoids

Reference: 01-11-2021

Salary: UKRI-level stipend

Closing date: 16/12/2021

About the role

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.

 

Experience required

  • Should have (or expect to achieve) a minimum of a 2.1 Honours degree in a relevant subject.

How to apply

To apply for an EASTBIO PhD studentship How to apply eastbio (eastscotbiodtp.ac.uk) follow the instructions below:

Check FindaPhD: PhD Programmes, Research Projects & Studentships in the UK & Europe (findaphd.com)  for our available projects and contact potential supervisors before you apply.

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 protected]

Download and send the EASTBIO Reference Form to your two academic/professional referees, and ask them to submit these directly to [email protected]  (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

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership http://www.eastscotbiodtp.ac.uk/how-apply-0. This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition fees only (Unfortunately we are unable to provide funding to cover the difference between UK and International fees). Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

 References:

  • Smith D, Price DRG, Burrells A, Faber MN, Hildersley KA, Chintoan-Uta C, Chapuis AF, Stevens M, Stevenson K, Burgess STG Innes EA, Nisbet AJ, McNeilly TN. (2021) The development of ovine gastric and intestinal organoids for studying ruminant host-pathogen interactions. Frontiers Cellular and Infection Microbiology. doi:3389/fcimb.2021.733811
  • Duque-Correa MA, Schreiber F, Rodgers FH, Goulding D, Forrest S, White R, Buck A, Grencis RK, Berriman M. Development of caecaloids to study host-pathogen interactions: new insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum. International Journal for Parasitology. doi: 10.1016/j.ijpara.2020.06.001

Supervisors

Dr Dan Price https://moredun.org.uk/people/staff-directory/dan-price

Dr David Smith https://moredun.org.uk/people/staff-directory/david-smith-fellow

Dr Neil Mabbott [email protected]

Dr Alasdair Nisbet https://moredun.org.uk/people/staff-directory/alasdair-nisbet

Dr Tom McNeilly https://moredun.org.uk/people/staff-directory/tom-mcneilly

 

 

Staff benefits

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