Testing the effect of aspirin on colonic organoids from people with Lynch syndrome

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Number of Honour Places Available
1
Department
Clinical Pathology
Supervisor Email Number Webpage
Fred Hollande frederic.hollande@unimelb.edu.au 0385597023 Personal web page
Eric Jihoon Joo ji.joo@unimelb.edu.au Personal web page

Project Details

Lynch Syndrome (LS) is a relatively common genetic condition with a prevalence of ~1 in 300.  LS is caused by germline mutations in the DNA mismatch repair genes and individuals affected with LS are predisposed to various cancers, most frequently colorectal cancer (CRC).  Aspirin and other non-steroid anti-inflammatory drugs (NSAIDs), which are inhibitors of COX enzymes, have shown a protective effect against CRC, including in Lynch syndrome related CRC. Regular users of aspirin are shown to have reduced CRC incidences by up to 50% hence often prescribed in individuals with LS.  Human intestinal epithelial organoid (IEO) has become a powerful translational research tool for understanding the colorectal biology and treatment development. The effect of aspirin and other NSAIDs has never been studied in the IEO model. This project hypothesises that there are stable changes in DNA methylation that are induced by aspirin and this can be detected in the IEO model.  DNA methylation can “switch” genes on and off without changing DNA sequences and is one of the epigenetic mechanisms most sensitive to environments.  In this project, the student will be involved in developing IEOs from colonic mucosa biopsies from colonoscopy of individuals affected with LS.  The IEOs will be treated with aspirin and other drugs and the methylomes and the transcriptomes will be assessed by the Infinium HumanMethylationEPIC and RNA-Seq at multiple time points to measure aspirin-inducible DNA methylation and gene expression changes.  A stipend for this project is available to the selected student.



Faculty Research Themes

Cancer

School Research Themes

Cancer in Medicine



Research Opportunities

PhD, Masters by Research, Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Clinical Pathology


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