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Investigating the impact of epigenetic processes in colorectal cancer

A postgraduate research opportunity at the University of Otago.

Details

Close date
Sunday, 27 February 2022
Academic background
Sciences, Health Sciences
Host campus
Christchurch
Qualification
Honours
Department
Pathology and Biomedical Science (Christchurch)
Supervisor
Professor Margreet Vissers

Overview

Epigenetics involves the chemical modification of DNA or histones, and leads to differential gene expression, influencing individual characteristics and propensity for disease.

Methylation of cytosine residues was the first identified epigenetic mark on DNA, and has been shown to play a major role in the regulation of gene transcription. Methylcytosine (5mC) patterns are altered in cancer, with hypomethylation altering genome stability and hypermethylation being associated with repression of tumour suppressor genes, cancer initiation and progression.

The presence of 5mC can be modified by the activation of the ten-eleven translocase enzymes (TET1, TET2 and TET3) that sequentially oxidise 5mC to hydroxymethylcytosine (5hmC), formyl-cytosine (5fC) and carboxylcytosine (5caC). The activity of the TET enzymes may influence the epigenetic regulation of cancer cells and could affect cancer outcomes.

The TET enzymes belong to the family of iron (II) and 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDD), an extended family of enzymes that contain an active site Fe(II) atom, and utilise 2-oxoglutarate and oxygen to catalyse the oxidation of C-H bonds in a multitude of organic targets. The substrate requirements indicate that the 2-OGDDs will be responsive to changes in cell metabolism. With an absolute dependence on oxygen and 2-OG, a Krebs cycle intermediate, changes in the cellular microenvironment and mitochondrial function can affect enzyme activity.

In addition, the catalytic cycle involves the redox cycling of the active site Fe from Fe(II) to Fe(IV) and conditions that affect Fe supply result in decreased activity. Ascorbate (vitamin C) is also an essential co-factor, with the enzymes showing a decided preference for this compound.

Preferred student expertise:

This project would suit a student with a good background in cell biology and biochemistry. The project will use latest technologies for live cell imaging. Although experience in microscopy is not essential it would be important for the student to have an interest in cell biology and imaging technologies. Good computer skills are required for this project.

Further information:

This is one of a number of projects on offer for the 2022 intake of BBiomedSc(Hons) at the University of Otago, Christchurch campus.

Contact

Professor Magreet Vissers
Email   margreet.vissers@otago.ac.nz