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Investigating the role of bioactive lipids in regulating enteric infection and cancer development.


Cardiff School of Biosciences

Dr Katherine Smith , Friday, April 16, 2021 Funded PhD Project (UK Students Only)
Cardiff United Kingdom Cancer Biology Immunology Parasitology

About the Project

Start date: 1st October 2021

Essential polyunsaturated fatty acids (PUFAs) derived from the diet play an important role in regulating intestinal homeostasis and the development of inflammatory disorders, such as inflammatory bowel disease and inflammation-associated colorectal cancer. PUFAs are of importance for intestinal health, as they can modify intestinal membrane composition, regulate intestinal epithelial cell proliferation and apoptosis, as well as mediate numerous signalling events, through the production of bioactive lipid mediators.

Although the balance of omega-3 PUFA to omega-6 PUFAs in the diet appears to play an important role driving intestinal inflammation and cancer, there are many unanswered questions related to the regulation of bioactive lipid mediator production, as well as their mode of action. Some of these interesting questions include the contribution of intestinal immune cells, epithelial cells and the microbiota to lipid mediator production, the impact of bioactive lipids on immune homeostasis, the initiation of inflammation-associated colorectal cancer, as well as the ability to respond to chronic gastrointestinal infections, such as helminths.

In this project we will use of a well-established pre-clinical model of colitis-associated colorectal cancer, robust murine models of human helminth infection as well as transgenic models, knockdown approaches and microbiome depletion. Changes to the microbiota will be profiled through 16s rRNA sequencing and bioinformatic analysis. Changes to bioactive lipid mediators will be profiled with state-of-the-art mass spectrometry, while changes in immune homeostasis, the initiating events of colorectal cancer and the anti-helminth immune response will be assessed by flow cytometry, immunohistochemistry, qPCR, ELISA or through egg and adult worm counts. The bioactivity of the lipid mediators identified will be assessed in cell-based assays, which will include use of state-of-the-art live imaging.

The outcome of these investigations will generate new information including identification of the host mechanisms that control the risk of developing colitis-associated colorectal cancer. Furthermore, the project has potential to interrogate the role of PUFA metabolism in homeostasis and responses to gastrointestinal helminth infections.


Funding Notes

This PhD studentship is fully funded for 3 years, which includes stipend, tuition fees and consumable costs. Starting date 1st October 2021.
In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the application system, click the ’Institution Website’ button on this advert).There is a box at the top right of the page labelled ‘Apply’.

References

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a Biomedical Sciences, Biochemistry, or one of the medical/health sciences. A Masters qualification in a similar area would be an advantage.
Candidates with experience or an interest in Bioanalysis are encouraged to apply.
HOW TO APPLY
In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the application system, click the ’Institution Website’ button on this advert).There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2021). This will take you to the application portal.
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In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select ’I will be applying for a scholarship/grant’ and specify that you are applying for advertised funding from Cardiff University School of Biosciences.

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