Friday | 5 December, 2008
Australian Biotechnology News
Above and beyond DNA
After becoming an epigenetics convert four years ago at Lorne and winning the Eppendorf Young Investigator’s Award there two years ago, Dr Jeff Craig returns to Lorne in 2008 as an invited speaker to present the fruits of his conversion.
Fiona Wylie 19/02/2008 16:01:18

Epigenetics, literally meaning 'above the DNA', is the study of how proteins and other molecules that bind our DNA and chromosomes can change gene expression without changing the DNA sequence. Cells use epigenetic changes during embryonic development to regulate gene expression as needed, and to prevent genetic problems through life.

Faulty epigenetics have been linked to many diseases, including cancer and psychiatric disorders, and mounting evidence indicates that diet and other environmental influences could directly affect epigenetics. The challenge for researchers in this field is to study these phenomena meaningfully, on both the single-gene and genome-wide scale, and to ascertain how epigenetic changes could impact on health status in both children and adults.

In 2006, Jeff Craig set up an epigenetics laboratory at the Murdoch Children's Research Institute in Melbourne, in partnership with Dr Richard Saffery. Their aim was to investigate epigenetic components of childhood and adolescent disease and to identify epigenetic factors such as DNA methylation and histone modification that contribute to human disease.

After a set-up phase and some pilot studies, work at the new lab is just starting in earnest, inspired by two bodies of evidence. "Firstly, we became really interested in the Developmental Origins of Health and Disease (DOHaD) theory proposed by researchers in the UK several years ago," Craig says. "This emerging field is based on the hypothesis that chronic illnesses such as heart disease, diabetes, osteoporosis, mental health, cancer and obesity originate during foetal development or shortly after birth."

To test the hypothesis, infants with low birth weight for gestational age were followed through life and found to have a much higher rate of these complex diseases, particularly cardiovascular disease. Craig was fascinated by these results from the viewpoint of epigenetics, and this interest was stimulated further by recent animal experiments showing that alterations in the foetal environment, such as in diet or stress levels, could influence the health and gene expression of the offspring.

The second major influence on Craig and his team was a low-resolution study by a group in Spain that compared an epigenetic 'barcode' within pairs of twins. The Spanish scientists compared old and young twins and found that DNA methylation states were more different between older twins than between the younger ones. Craig and his colleagues were intrigued to see if the same changes could be measured at birth and thereafter, which nobody had looked at so far.

So, they set about investigating the epigenetic differences between newborn twins, looking at the correlation of maternal nutrition with epigenetics at birth and into early life. "Twins are the best model to study this link as they share similar, but not identical, environments, and some share identical genetics," he says.

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