About the Project
Number of awards
1
Start date and duration
October 2020 for 3 years
Overview
Prevention is better than cure, and it has been shown that aspirin can significantly reduce the incidence of colorectal cancers if taken regularly. However, its use in older populations is limited by the adverse risk/benefit ratio, in particular an increased risk of gastrointestinal bleeds and cancer deaths in those over 70 years of age. The molecular mechanisms underlying the increased risk of these pathologies with age are currently unknown.
One of the common features of the ageing intestinal epithelium is an increase in the frequency of crypts with mitochondrial dysfunction. Mitochondria are the powerhouses of the cells, responsible for a number of essential cellular functions including ATP production through oxidative phosphorylation, execution of apoptosis, and regulation of the production of reactive oxygen species. We hypothesise that dysfunctional mitochondria may both contribute to the development of neoplastic lesions and impact on the integrity of the gut wall, making it vulnerable to the adverse effects of aspirin.
In this PhD project, the student will investigate the impact of aspirin on both the normal intestinal mucosa of mice, with and without genetically engineered mitochondrial dysfunction, and on intestinal cancer development. In addition, they will compare the standard aspirin used in the clinic with a newly formulated ‘liquid aspirin’ where the salicylate is linked to a short-chain fatty acid, to look at its effect on the normal gut wall and in the intestinal cancer model. Short chain fatty acids are a recognised energy source in the gut and have been used independently as a therapeutic intervention to prevent cancers. It is possible that this will provide the basis for a clinical trial of liquid aspirin in an older cohort to provide more effective and safer cancer prevention.
The student will utilise a number of cellular and molecular biology techniques including 3D organoid culture, immunofluorescence, histology, RNA-Seq, RT-PCR, confocal microscopy and in vivo imaging.
Sponsor
The Barbour Foundation
Name of supervisor(s)
Dr Laura Greaves (https://bit.ly/3bPymQB)
Dr Michael Jackson (https://bit.ly/37Igeop)
Professor Sir John Burn (https://bit.ly/2SK51j2)
Eligibility Criteria
You must have, or expect to achieve, at least a 2:1 honours degree or international equivalent, in a subject relating to the biological sciences, including: cell biology, biomedical sciences and genetics. A further qualification such as an MRes is advantageous.
How to apply
You must apply through the University’s online postgraduate application system (https://bit.ly/2wsUMXn).
Only mandatory fields need to be completed. However, you will need to include the following information:
•insert the programme code 8300F in the programme of study section
•select ‘PhD in the Faculty of Medical Sciences(full time) - Biosciences’ as the programme of study
•insert the studentship code bi003 in the studentship/partnership reference field
•attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code bi003 and state how your interests and experience relate to the project
•attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications
Contact
[Email Address Removed]
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