Temporal DNA methylation changes associated with serrated pathway tumourigenesis identified from human intestinal organoids

This project will improve our understanding of the serrated pathway and contribute to identifying molecular drivers of transformation to colorectal cancer that will be used a biomarker for prevention.

The development of a colorectal cancer (CRC) is preceded by pre-cursor/pre-malignant lesion called a polyp.

There are two major types of polyps defined by histological features namely the adenomatous polyp and the serrated polyp.  The serrated polyp to CRC pathway is characterised by unique molecular features including genome-wide changes in DNA methylation, however, the key DNA methylation changes that drive serrated polyp evolution and tumourigenesis are not currently known. Human intestinal epithelial organoids (IEO) have become a powerful translational research tool for understanding the colorectal biology and treatment. 

In this project, the student will develop IEOs from colonic mucosa and serrated polyp biopsies collected from colonoscopy of people with serrated polyposis syndrome (a condition characterised by developing 10s-100s of serrated polyps throughout the bowel).

The DNA from IEOs will be collected at different timepoints and snapshots of genome-wide DNA methylation profiles will be taken using the Infinium Human Methylation EPIC to determine DNA methylation changes associated with the initiation and progression of CRC tumourigenesis.

The outcomes from this project will improve our understanding of the serrated pathway and contribute to identifying molecular drivers of transformation to CRC that will be used a biomarker to prevent CRCs arisen via this specific tumourigenic pathway.

This project will develop expertise in molecular genetics/biology, histology, bioinformatics and statistical analysis.  A stipend for this project is available to the selected student.

Contact and more information

Primary supervisor

Dr Eric Joo
ji.joo@unimelb.edu.au

Co-supervisor

Professor Frédéric Hollande
frederic.hollande@unimelb.edu.au

Co-supervisor

Associate Professor Daniel Buchanan
daniel.buchanan@unimelb.edu.au

Colorectal Oncogenomics Group
University of Melbourne Centre for Cancer Research and Department of Clinical Pathology

Level 10, Victorian Comprehensive Cancer Centre