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Formed in 2015, EpiCSA has brought together epigenetics researchers from diverse disciplines with a number of workshops and meetings to date, the first Annual EpiCSA Research Meeting being a major highlight. The meeting was held at the auditorium of the South Australian Health and Medical Research Institute.
Dr Tina Bianco-Miotto, EpiCSA Chairperson, who led the organisation of the meeting, said, “Our first annual research meeting was a wonderful success. We were honoured to have leading epigenetic researchers speaking, and the event also gave early career researchers and students the opportunity to showcase their work.”
AEpiA was delighted to sponsor two awards at the event: The award for Best Student Poster Talk was presented to Saira Ali of Flinders University, and The Best Student Poster prize was awarded to Paniz Tavakoli of CSIRO and University of Adelaide.
The title of Saira’s poster was Epigenetic regulation of gene expression in colorectal cancer (CRC) cells, and in her talk she discussed her work using high-throughput functional screens to identify microRNAs that might sensitise CRC cells to the anti-tumorigenic molecule butyrate. Saira is currently validating a number of microRNA targets that may have potential as tumour suppressors.
Paniz’s poster was entitled Folate deficiency increases guanine-quadruplexes (G4) frequency and DNA damage in Werner syndrome. Werner syndrome is a rare autosomal disease characterised by the premature onset of several age-associated pathologies, and Paniz presented her work characterising the links between folate deficiency and the presence of DNA G4 structures and altered DNA methylation profiles in cells from patients with this condition.
Saira and Paniz were kind enough to write about some of the highlights of the EpiCSA meeting for them – please read them below.
AEpiA congratulates EpiCSA on another successful event, and we look forward to hearing more in 2017.
Saira Ali writes:
Attending the EpiCSA Annual Research Meeting 2016, I was very impressed by the amazing epigenetics research being performed by our local students and researchers. There were two talks by Benjamin Mayne and Kavita Panir, both from University of Adelaide, that particularly drew my attention.
Benjamin spoke about DNA methylation changes observed in the placenta of pregnant women. I found his research very interesting because Benjamin collated DNA methylation data from publicly available data sets and he identified methylation changes in CpG sites that could be used to predict the gestational age of the placenta. This highlights how important it is to share your data because someone else may ask a completely different question from you and discover something novel from the same data set!
Kavita spoke about the effect of knocking out miR-223 in mice on the formation of endometriosis-like lesions. Kavita’s talk was interesting because she demonstrated that the absence of this miRNA affects the size and weight of the lesions formed in the miR-223 knockout mice. For me it is really interesting to see miRNA research from people studying different diseases and realise how different the role of an individual miRNA can be in different tissues. This same miRNA has been associated with poor prognosis in patients with colorectal cancer (my area of study) and tumour metastasis.
Paniz Tavakoli writes:
Maxime François (CSIRO, Health and Biosecurity) gave an elegant presentation on the epigenetic importance of G-quadruplexes, which are DNA tetra-stranded secondary conformations, in a context of human diseases and nutrition. It has been proposed that these structures can affect the stability of our genome and have been found to be elevated in aging disorders, mild cognitive impairment in particular. His results showed that exposing cells to folate deficiencies had repercussions on the appearance of these structures and genome stability, emphasising the important roles of nutrients at the cellular level.
This talk grabbed my attention by introducing quantitative imaging, a different approach for measuring G-quadruplexes other than bioinformatics and computational biology methods mentioned in previous presentations that day. As stated, this developed technique requires precise targeting of these structures within human DNA by a specific antibody and was shown to be adaptable for high-throughput. Since sequencing is expensive and requires expertise in bioinformatics, this method may be a powerful tool for epigenetic studies.
Saira Ali and EpiCSA’s Tina Bianco-Miotto
Paniz Tavakoli and EpiCSA’s Tina Bianco-Miotto
First Annual EpiCSA Research Meeting organisers
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.