annual report 2013
cell biology KEY PROTEIN LINKED TO CANCER IDENTIFIED
MATERNAL BMI PREDICTS TYPE 2 DIABETES IN CHILDREN
Researchers have made landmark discoveries studying the IGFBP-2 protein. Not only is this protein important in the normal insulin-like growth factor (IGF) pathway, but it is also involved in cancer cell growth. This work is likely to translate into more effective cancer therapies.
A team of international researchers, including Dr Matt Sabin (left) from the Institute, found a mother’s body mass index (BMI) can be used as a predictor for the later development of type 2 diabetes in her children, and is a stronger predictor than genetic data.
The Hormone Research group, led by Dr Vincenzo Russo and Professor George Werther, is internationally recognised for its leading work in the insulin-like growth factor field. The IGF system is ubiquitous during human embryonic life, early postnatal development and in adulthood. It controls cellular maintenance and a number of essential metabolic functions in most organs and tissues. Impairment of the IGF system occurs in disease state and malignancies, and elevation of the IGFBP-2 gene is consistently reported in major aggressive cancers. These include paediatric brain tumours and other common tumours affecting the Australian population, such as prostate and breast cancer. Researchers were able to demonstrate the pathways whereby IGFBP-2 could dramatically increase the rate of cancer cell growth and accelerate their spread to other sites where they normally wouldn’t grow. The study was the first to identify a specific region of the protein that is required for entry in the cell nucleus and for binding to genes that regulate cancer cell growth. When the team introduced changes to this region, the protein could not enter the nucleus and was rendered unable to activate the cancerpromoting genes. The team is now working toward the development of anti-cancer therapeutic molecules targeting IGFBP-2 activity in cancer cells. The study was published in the prestigious journal Oncogene.
Researchers studied more than 1800 children for more than 20 years and found not only did maternal BMI predict the later development of type 2 diabetes in offspring, but that the association was independent of other childhood factors, including genetics. Researchers also found a risk predication model based on both the child and mother’s BMI status was more accurate in predicting adulthood type 2 diabetes compared with an approach including only the child’s BMI data. They found no association between the father’s BMI and the later development of type 2 diabetes in the offspring. The study showed maternal BMI at recruitment of the child to the study, as well as the child’s own BMI, systolic blood pressure and genetic risk score for type 2 diabetes were all significantly associated with increased risk. Interestingly, fruit consumption showed inverse associations. The study was published in the Journal of Pediatrics.
EPIGENETICS CHANGE RAPIDLY IN FIRST YEAR OF LIFE The way our genes are activated changes rapidly when we are infants, a study by the Institute found. Researchers studied the epigenetic “switches” that regulate gene activity in 15 sets of twins at birth and at 18 months of age. The study, which was published in Genome Biology, found widespread epigenetic change in the genome within the first 18 months of life. Epigenetic gene switches help to direct development and ageing but can also be influenced by the environment, particularly in early life. Focusing on DNA from cheek cells, researchers found that one third of the locations they looked at had changed their epigenetic state between birth and 18 months of age, with the regions furthest from genes changing the most.
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< TWINS REBECCA & ZOE WITH MUM VICKI KOUTS
This supports the idea that our genomes are most susceptible to the environment in the first 1000 days of life. Researchers also found twins can become more epigenetically different with age, but unexpectedly that some twins can become more epigenetically similar. Researchers say this may be because some twins have very different environments in the womb, but very similar environments after birth.
Hirschsprung disease is a disorder of the bowel in which the last part of the large intestine lacks a nervous system. The absence of the nervous system means that the bowel is unable to coordinate its normal muscular activity, called peristalsis, which propels food along the intestinal tract. Without treatment the affected portion of the bowel forms a physiological block to the movement of food.
The researchers’ next focus will be on specific diet and lifestyle factors of mums and babies, which may have the capacity to change their epigenetics and possibly influence future health.
The novel treatment developed and trialled by researchers involves reintroducing a new enteric nervous system in the non-functioning part of the bowel. Nerves can be obtained from nerve stem cells, but the question is: how do you get them into the bowel? The study, published in the Biomaterials journal, described a successful method of introducing nerve stem cells into the bowel of mice. In this treatment the nerve stem cells are grown on a biodegradable mesh, made by Monash Universitybased polymer chemists, and introduced into the bowel by wrapping the outside of the bowel. The next step for our researchers is to see if the finding translates when using human nerve stem cells in the patient’s own tissue.
NOVEL TREATMENT POSSIBILITY FOR HIRSCHSPRUNG DISEASE Our researchers are working on an innovative treatment for Hirschsprung disease, which could mean children would not have to undergo surgery for the condition. While the current surgical treatment is life-saving, many children have ongoing problems which persist into adolescence and sometimes into adulthood.
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