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How does low genetic diversity impact pathogen emergence in a vulnerable island species, the Tasmanian devil

  • Full or part time

    Dr P Skipp
  • Application Deadline
    Friday, January 04, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Project Rationale :
Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil, an island marsupial which has suffered drastic population decline due to an older, more widespread contagious cancer, Devil Facial Tumour 1 (DFT1)2. The two tumours are both spread by direct transmission of tumour cells, causing the growth of large tumours around the face.

The Major Histocompatibility Complex class I (MHC-I) genes are key to the immune response against infected and malignant cells. The MHC-I molecule binds a peptide, derived from a self or non-self protein that is presented to immune cells, signaling that the cell is healthy, infected or malignant. Polymorphism in MHC-I genes allows a population to respond to nearly any pathogen by presenting an array of non-self peptides. Thus, loss of genetic diversity at these genes could leave a population vulnerable to disease. However, the mechanisms that determine resistance or susceptibility to pathogens in wild populations are not well understood1.

We have recently found that DFT2 cells express MHC-I molecules, but tumour cell transmission still occurs3. We will test the hypothesis that a lack of genetic diversity at MHC class I genes reduces the peptide repertoire, allowing emergence of a contagious cancer.

Methodology:
1. Do all DFT2 tumours express MHC-I?
Immunohistochemistry and ImageJ will be used to quantify MHC-I expression in 20-25 DFT2 biopsy samples collected monthly from 2015 onwards. We will monitor any changes to MHC-I expression that reflect evolution of the tumour and if found, the rate of MHC-I loss. We will define the MHC-I alleles expressed by DFT2 cells by sequencing full MHC-I mRNA transcripts.
2. How diverse are MHC-I genes in the host population?
Loss of genetic diversity in MHC-I genes in specific populations may be allowing contagious cancers to emerge. Next Generation Sequencing will be used to assess polymorphism in MHC-I alleles from the population where DFT2 emerged (50 animals).
3. Do devil MHC-I molecules have a reduced peptide repertoire?
The immunopeptidome encompasses all peptides presented by a cell’s MHC-I molecules and determines the ability of a population to respond to a pathogen. Using established techniques in the Siddle and Skipp labs (immunoaffinity purification of MHC-I and mass spectrometry) we will sequence the MHC-I bound peptides from individuals with representative MHC-I genotypes in the population. The Siddle lab has recently defined the immunopeptidome of DFT2 and this will be used to compare the tumour and host immunopeptidomes.

Training:
The INSPIRE DTP programme provides comprehensive personal and professional development training alongside extensive opportunities for students to expand their multi-disciplinary outlook through interactions with a wide network of academic, research and industrial/policy partners. The student will be registered at the University of Southampton and hosted at the School of Biological Sciences. Specific training will
include:
This project involves a combination of advanced molecular techniques and field work experience, a key combination for developing future conservation and environmental scientists. The student will have the opportunity to apply these developing skills to a unique disease affecting a species in danger of extinction, but these skills are highly applicable to studying emerging pathogens and wildlife immunology more broadly.

Specifically, the student will have access to world class proteomics facilities and proteomics supervision, next generation sequencing and bioinformatics training. They will work closely with postdoctoral scientists in the Siddle and Skipp labs with experience in proteomics and generating immunopeptidomes from MHC molecules. There is also training and experience in field work (trapping animals, collecting and processing samples) which will be conducted in the Channel region of Tasmania with Dr Hamede who has 10 years expertise working with Tasmanian devils.

Funding Notes

You can apply for fully-funded studentships (stipend and fees) from INSPIRE if you:
Are a UK or EU national.
Have no restrictions on how long you can stay in the UK.
Have been 'ordinarily resident' in the UK for 3 years prior to the start of the project.

Please click View Website for more information on eligibilty and how to apply

References

1. Radwan J, Biedrzycka A, Babik W (2010) Does reduced MHC diversity decrease viability of vertebrate populations? Biol Conserv 143:537–544.
2. Siddle HV. Cancer as a contagious disease (2017) HLA, 89(4):209-214
3. Caldwell A., Coleby R., Tovar C., Stammnitz MR., Kwon YM., Owen R., Tringides M., Murchison EP., Skjødt K., Thomas GJ., Kaufman J., Elliott T., Woods G, and Siddle HV. (2018) The newly-arisen Devil Facial Tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer. eLife; 7:e35314 DOI: 10.7554/eLife.35314

How good is research at University of Southampton in Earth Systems and Environmental Sciences?

FTE Category A staff submitted: 68.62

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