Latest AEpiA news
Australian epigenetics researchers have been busy this year! We thought we’d share some of the publications AEpiA members have told us about:
New research from the Florey Institute of Neuroscience and Mental Health at the University of Melbourne shows that raising stress hormone levels in male parental mice leads to a predisposition to anxiety and depression-related disorders in the next two generations of offspring.
In the study, led by Prof Tony Hannan, treatment of male mice with corticosterone caused changes in anxiety levels and depression-like phenotypes in F1 and F2 offspring, with different effects in males compared to females. Analysis of the the small RNA profile in sperm of the corticosterone-treated mice identified three microRNAs that are likely to mediate these physiological effects. Their findings were published in Translational Psychiatry in June. You can read more on the Florey Institute website or read the full text pdf here.
A study led by Prof Sue Clark and Dr Clare Stirzaker from the Garvan Institute of Medical Research in Sydney revealed novel insights into gene silencing in cancer.
Their work showed that MBD2 promotes the maintenance and spread of DNA methylation at key regulatory regions in prostate cancer cell lines, and using tumour samples from The Cancer Genome Atlas (TCGA), they demonstrated significant hypermethylation mediated by MBD2 in the same genomic regions. This ‘re-writing’ of the cancer methylome by MBD2 is therefore likely to be relevant to the clinical progression of cancer. This study was published in Oncogene in September. Read what Dr Stirzaker and Prof Clark have to say on the Garvan Institute website.
Researchers from Queensland University of Technology have demonstrated that salivary DNA methylation has the potential to detect early-stage tumours in head and neck squamous cell carcinoma (HNSCC) patients. The study, led by A/Prof Chamindie Punyadeera, validated a panel of tumour suppressor gene methylation in saliva samples collected from HPV-positive and HPV-negative head and neck cancer pateints compared with healthy controls. As the typical five year survival rate for HNSCC patients is less than 40 %, the potential for early detection has important clinical implications. Their study was published in BMC Cancer last month.
In a study published in Genome Biology this month, researchers including Drs Ruth Pidsley, Elena Zotenko and Tim Peters from the Garvan Institute of Medical Research performed a thorough examination of the pros and cons of Illumina’s EPIC BeadChip microarray for whole-genome DNA methylation profiling.
Their study concludes that this new technology is a significant improvement over previously available tools, and their findings will be a highly informative resource for researchers worldwide.
(L-R) Elena Zotenko, Ruth Pidsley and Tim Peters
Image Credit: Christoph Bock/CeMM
An international team of scientists, including AEpiA researchers at the Garvan Institute of Medical Research in Sydney, has shown that DNA methylation analysis is a mature technology that is ready for clinical use. Their study was reported in Nature Biotechnology last month.
The study was published co-ordinately with three other papers in Nature Biotechnology and Nature Communications. Conducted in the context of the European BLUEPRINT Project and the International Human Epigenome Consortium (IHEC), the four papers together mark the feasibility of epigenetic analysis for clinical diagnostics and personalised medicine, in cancer and beyond.
This study, a benchmarking analysis comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use was coordinated by BLUEPRINT and led by Christoph Bock at the Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM; Vienna). Thirty-two reference samples were analysed in 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays.
In many diseases, including cancer, the epigenetic control of the genome is heavily distorted. By measuring these alterations, a detailed picture of disease-specific changes emerges, which can help distinguish disease subtypes or identify suitable treatments. To date, however, little epigenetic testing has been carried out in the clinic.
Prof Sue Clark from the Garvan Institute said, “What we wanted to do as part of the International Epigenome Consortium was to carry out a wide-ranging technology comparison – to look in detail at the many DNA methylation assays now in existence, and to compare their accuracy and robustness in a systematic fashion.”
Prof Sue Clark, along with Dr Clare Stirzaker, Dr Shalima Nair, Wenjia Qu and Aaron Statham, compared two DNA methylation tests they had previously optimized: amplicon bisulphite sequencing (AmpliconBS) and mass spectrometric analysis of DNA methylation (EpiTyper). Both assays have their roots in bisulphite-based methods developed by Prof Clark in the 1990s, which were quickly adapted as the gold standard at the time.
Their investigation found that AmpliconBS is the best choice for assaying dozens of genomic regions in parallel, while EpiTyper provides the highest sample throughput.
The overall study, which was published in Nature Biotechnology, concludes “the accuracy and robustness, discriminatory power, cost structure and practical feasibility of current DNA methylation assays are sufficient for large-scale validation studies and epigenetic biomarker development.”
“Epigenetic tests have a key role to play for making precision medicine a clinical reality. Epigenetics captures part of each cell’s individual history, and it can predict how cancer cells will react to drug treatment. This can be very useful for personalized therapy,” explained Christoph Bock, Principal Investigator at CeMM.
DNA methylation analysis is ready for development for diagnostics, personalised therapies and many other clinical applications.
Watch our video below to find out more about the use of DNA methylation as Biomarkers.
You can watch more videos on our What is Epigenetics page.
A study led by researchers at the Victor Chang Cardiac Research Institute in Sydney has revealed that obese male mice can pass on metabolic phenotypes not only to their children, but also to their granddchildren.
Their work was published online in the journal Molecular Metabolism last month and has significant implications if it translates to humans.
While it is understood that metabolic phenotypes induced by parental obesity can be passed from one generation to the next, independent of the inherited DNA sequence, this study is the first to demonstrate that altered phenotypes can be inherited by a second generation, without direct exposure to obesity, even as germ cells.
In this study the researchers, who include AEpiA members A/Prof Cath Suter, Dr Jennifer Cropley and Dr Sally Eaton, demonstrate a potential mechanism of transgenerational inheritance involving small noncoding RNAs.
If these results translate to humans, they suggest that children of obese fathers, even if they themselves maintain heathy eating habits, can pass on metabolic dysfunction to their own children.
With almost two-thirds of the adult Australian population currently overweight or obese, this study attracted national as well as international media attention. The Sydney Morning Herald featured a news article about the study and Dr Cropley was interviewed for BBC world news.
Read more on the Victor Chang Cardiac Research Institute website.