A postgraduate research opportunity at the University of Otago.
- Academic background
- Health Sciences
- Host campus
- Pathology and Biomedical Science (Christchurch)
- Professor Margreet Vissers
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 cells to control cell phenotype and changes in gene expression. Removal of 5mC is achieved by the ten-eleven translocase enzymes (TET1, TET2 and TET3) that sequentially oxidise 5mC to hydroxymethylcytosine (5hmC), formyl-cytosine (5fC) and carboxylcytosine (5caC).
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.
The aim of this project is to investigate the effects of vitamin C availability on immune cell function. The project follows from our recent findings that boosting vitamin C intake can influence the generation of inflammatory cytokines by immune cells. We hypothesise that intracellular vitamin C affects gene expression in immune cells by epigenetic mechanisms. This hypothesis will be tested with two models of immune cells in vitro.
Preferred student expertise:
This project would suit a student with a good background in cell biology and biochemistry and an interest in genetics. The project will use cell biology techniques including flow cytometry, cell imaging technologies, mass spectrometry analysis of 5hmC levels, and RNA/DNA sequencing mechanisms. It would be important for the student to have an interest in cell biology, good computer skills and an aptitude for laboratory bench work.
This is one of a number of projects on offer for the 2023 intake of BBiomedSc(Hons) at the University of Otago, Christchurch campus.