Epigenetics Seminar Series 2020
We are delighted to bring you our new online Epigenetics Seminar Series, starting June 2020. We’ve planned a fantastic program, hosted by our Committee members, with a line-up of speakers from around Australia and overseas.
The Seminars will be held every four weeks, on Thursdays at 12 noon (AEST). Attendance is available to all Australian Epigenetics Alliance members – please join AEpiA for free or check your membership here.
A Zoom link will be sent to members prior to each meeting.
We enjoyed seeing many of you in June and July, and we look forward to seeing you again soon. Join in the chat on Twitter on #AEpiAseminar.
Thurs 22 Oct 2020*
10.00 – 10.45am* (AEST)
*Please note variation in date and time
Host: Dr Phillippa Taberlay
Professor Peter Jones
Van Andel Institute, USA
The whys and hows of DNA methylation
Peter’s laboratory discovered the effects of 5‑azacytidine on cytosine methylation and first established the link between DNA methylation, gene expression and differentiation.
Peter has helped pioneer the field of epigenetics, particularly its role in cancer, and helped develop novel cancer therapies. He has published more than 300 scientific papers and received several honors, including an Outstanding Investigator Award. He and Stephen Baylin shared the Kirk Landon Award for Basic Cancer Research from the AACR in 2009 and the Medal of Honor from the American Cancer Society in 2011.
Peter is a past President of the AACR and was elected a Fellow of the American Association for the Advancement of Science in 2009 and a Fellow of the Academy of the AACR in 2013. He was elected a member of the National Academy of Sciences of the USA in 2016, the American Academy of Arts and Sciences in 2017 and received an honorary D.Sc. from Stellenbosch University in 2018.
The whys and hows of DNA methylation
The origins and functions of DNA cytosine methylation remain enigmatic even after more than 50 years of intensive research. I will re-examine Bestor’s hypothesis that the original appearance of DNA methylation is linked to its ability to silence intragenomic transposable elements (TEs). Because cytosine methylation is inherently mutagenic and leads to diagnostic C-T transitions at methylated CpG sites in the germline, CpG depletion can be used as a surrogate for ancient methylation. We examined the distribution of CpG sites in the published whole genome sequences of 53 organisms. We found a strong correlation between CpG depletion and genome size which in turn is largely dependent on the quantity of TEs it contains. This finding provides evidence for an unrecognized function of DNA methylation which is to enable genome expansion. Given the importance of CpG methylation in this process, as well as in gene control in health and disease, the mechanisms for de novo methylation need to be understood in more detail. While the chemical mechanisms by which methyl groups are applied to the 5 position of the cytosine ring are well understood, this process is much more complicated in the context of chromatin particularly because nucleosomal DNA cannot be methylated by prokaryotic or eukaryotic methylases. We used the power of Cryo-EM to solve the structure of a tetrameric complex of two molecules each of human DNMT3A2 and DNMT3B3 bound to a nucleosome core particle. Unexpectedly, the catalytically inactive DNMT3B3 acts as an accessory protein for the potentially active DNMT3A2. This binding occurs through the involvement of the acidic patch on the nucleosomal histones whereas the DNMT3A2 is positioned on the linker DNA. The structure predicts that the nucleosome must be moved or remodeled for de novo methylation to occur as is predicted in several publications. Understanding the whys and hows of DNA methylation will help in understanding its multiple roles in health and disease.
Details to follow
Associate Professor Pilar Blancafort
Harry Perkins Institute of Medical Research
Reversing mesenchymal behaviour in cancer cells by targeted epigenetic editing
A/Prof Pilar Blancafort is a specialist in genome engineering and gene targeting, and her laboratory has pioneered the development of engineered DNA binding proteins to modulate the epigenetic state of cancer cells and delivery strategies for tumor targeting in pre-clinical studies.
After her undergraduate studies at the University of Barcelona, Pilar obtained her PhD in Biochemistry at the University of Montreal in Canada. She then moved to The Scripps Research Institute in California, USA for post-doctoral studies.
In 2005, Pilar established her laboratory at the University of North Carolina at Chapel Hill. In 2012, she moved her lab to The University of Western Australia and in she joined the Perkins as Head of the Laboratory in Cancer Epigenetics in 2014.
Pilar holds a Cancer Council of Western Australia, Australian Research Council Future Fellowship and a Wesfarmers Fellowship.
Professor Sudha Rao
Novel epigenetic driven re-invigoration: progress from mechanism to therapeutics in immuno-oncology
Professor Sudha Rao has extensive experience in transcriptional biology and genomic technologies that spans both pharmaceutical and academic settings. The primary focus of Sudha’s research group is to unravel complex epigenetic-signatures in the immune system, as well as to understand the deregulatory mechanisms operating in cancer settings.
Sudha obtained her PhD from the University of London, Kings College in 2000. During this period, she joined a team of scientists at Rhone Poulenc/Sanofi Pharma, both in UK and France. During this time, she was part of one of the first groups world-wide to establish the clinical genomics platform for therapeutics in the UK.
Sudha has developed close partnerships with global technology companies and established novel liquid biopsy clinical platforms, first of its kind in Asia, for non-invasive tracking of blood samples from cancer patients. She has attracted highly competitive NHMRC, ARC and commercial funding to advance her cancer work. Sudha’s work has yielded national and international patents for both novel diagnostics and therapeutics in the emerging arena of immune-oncology and this work has great potential for cancer patients.
Professor Jus St. John
The University of Adelaide
Professor Jus St. John is based in the Robinson Research Institute and The School of Medicine at The University of Adelaide. His research focuses on understanding how mitochondrial DNA is replicated and transmitted during development.
Jus uses a variety of assisted reproductive technologies and stem and tumour-initiating cell models to show how mitochondrial DNA replication is regulated in oocytes, embryos and undifferentiated and differentiating stem cells and why mtDNA replication is important to developmental outcome. His work indicates that the nuclear and mitochondrial genomes should be in synchrony for mitochondrial DNA replication and cellular differentiation to take place.
Jus has further shown that modulating the nuclear genome through, for example, DNA demethylation agents can impact on mitochondrial copy number. Likewise, modulating mitochondrial DNA copy number or haplotype can alter the global DNA methylation profiles of the nuclear genome. In cells that have established genomic balance, these actions can result in arrest whilst, in tumour-initiating cells, this can promote differentiation.
Dr Alyson Ashe
The University of Sydney
Insights into transgenerational epigenetic inheritance from C. elegans
Dr Alyson Ashe is an early career research fellow in the School of Life and Environmental Sciences at The University of Sydney. She is interested in all areas of epigenetics and small RNA molecules.
Alyson studies epigenetic regulation of gene expression: the interplay between the environment that an organism encounters during its lifetime, and the expression patterns of its genes. Importantly, these environmental signals can sometimes get passed between generations (Darwin was wrong!), and Alyson’s work is trying to understand how this occurs.
To do this Alyson mainly uses the model organism C. elegans, a small nematode worm, but is also branching out into other species such as the honey bee.