Online Epigenetics Seminar Series
Epigenetics Seminar Series 2022
We’re delighted to resume our online Epigenetics Seminar Series in March 2022. A wonderful program is being planned, hosted by our Committee members, with a line-up of speakers from around Australia and overseas.
The Seminars will be held monthly. 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 out with calendar invites to all our members.
Join in the chat on Twitter on #AEpiAseminar.
Many of our seminars will be recorded (with speakers’ permission), so if you miss one that you’d love to see, email us and we may be able to send you a link to the recording.
We extend many thanks to our generous sponsors this year.
A/Prof Luciano Martelotto
A brief overview of my favourite single cell and spatial epigenomics technologies
A/Prof LucianoMartelotto (B Biotech, PhD) has been recently appointed Head of the Single cell and Spatial-omics Development Lab at the Adelaide Centre for Epigenetics (ACE), South Australia ImmunoGENomics Cancer Institute (SAIGENCI). Prior to joining ACE/SAIGENCI, he was the Scientific Director of the Single Cell Laboratory at Harvard Medical School (HMS), Department of Systems Biology, Harvard University (USA). Luciano is also the Chief Technology Officer and Director of R&D of OmniScope, a health tech company specialized in high throughput immune profiling at single cell level.
Luciano has a robust interdisciplinary scientific background, specialising in molecular biology and biochemistry with a strong background in technology and engineering. His diverse scientific background stems from working in a wide range of fields encompassing plant genetics, microbiology, cancer biology and genomics, and has shaped his capacity to learn, create, develop, and apply technologies across multiple disciplines.
Luciano is a recognised world leader in development and exploitation of advanced -omics technologies including the single cell and spatial proteomics analyses described in this research proposal. Luciano’s laboratory is constantly evolving and developing technologies for the wider scientific community.
Seminar: A brief overview of my favourite single cell and spatial epigenomics technologies
In the past decade, assays that profile different aspects of the epigenome have grown exponentially in number and variation. The diversity of single cell and spatial epigenomic assays has expanded in the recent years through both adapting traditional low-throughput techniques, as well as the invention of novel technologies for epigenome-wide high-throughput experiments. It has thus become increasingly critical to choose the right type of assay depending on the goals, context, and applications in mind. In this talk, I will provide an intuition of my favourite technologies applied to single cell and spatial epigenomics.
A/Prof Jason Lee
Details coming soon.
Dr Hamish King
Single-cell genomics to understand gene regulatory potential in the human immune system
Dr Hamish King completed his undergraduate and Honours at Flinders University in Adelaide, before moving to the United Kingdom to undertake his PhD training in molecular epigenetics at the University of Oxford with Prof Rob Klose.
While there, Hamish studied how gene expression is regulated by chromatin-modifying complexes, and how sequence-specific transcription factors cooperate with chromatin remodellers to access and bind the genome. Following his PhD, Hamish was a Sir Henry Wellcome Postdoctoral Fellow in the lab of Dr Louisa James at the Blizard Institute, Queen Mary University of London, where he studied the transcriptional and epigenetic regulatory networks that determine B cell identity and function in the human immune system. As part of this fellowship, Hamish also worked closely with Dr Sarah Teichmann (Wellcome Sanger Institute, Cambridge) and Prof William Greenleaf (Stanford).
Building on his recent discoveries, Hamish recently joined the Walter and Eliza Hall Institute as a Group Leader in February 2022, where he is focused on understanding the molecular mechanisms that underpin global and locus-specific epigenetic regulation of gene expression in human B cell maturation using cutting edge single-cell and epigenomic approaches.
Seminar: Single-cell genomics to understand gene regulatory potential in the human immune system
B cell-mediated immune responses and memory form in secondary lymphoid organs, such as the tonsils, lymph nodes or spleen and form a major arm of the adaptive immune system to fight and remember infections. During this process, B cells undergo affinity maturation in the germinal centre reaction and errors at this stage can lead to either defective immune responses or contribute to autoimmune disease. Many questions remain about the dynamic cellular states involved in both normal and disease-related B cell maturation, including the gene regulatory networks that underlie key cell fate decisions and phenotypes. We have generated a comprehensive roadmap of human B cell maturation in a model secondary lymphoid organ by defining the gene expression, antibody repertoires, and chromatin accessibility of diverse B cell states at single-cell resolution. We have used this roadmap to reconstruct gene expression and transcription factor dynamics during B cell activation and to interpret potential regulatory impact of genetic variants implicated in autoimmunity. We predict that many autoimmune-linked GWAS variants exhibit their greatest regulatory potential in germinal centre-associated cell populations, providing new insights into the cellular and genetic causes that may underpin autoimmune disease.
Dr Louise Bicknell
Mutations in Histone H4 underlie a novel neurodevelopmental disorder
Dr Louise Bicknell is a human geneticist and former Rutherford Discovery Fellow at the University of Otago, who specialises in understanding the mechanisms of disease affecting growth and development.
Louise completed her PhD at the University of Otago in 2007, before moving to Edinburgh to undertake post-doctoral studies with Prof Andrew Jackson, at the Institute of Genetics and Molecular Medicine, University of Edinburgh. While in Edinburgh, Louise undertook multiple high-profile studies exposing the genetic causes of growth disorders. Since establishing her own lab at Otago in September 2015, her research has expanded into more general developmental disorders, with a recent focus on neurodevelopmental disorders featuring mutations in histone proteins and other epigenetic machinery.
Louise is Co-Director of Genetics Otago, and was awarded the Rowheath Trust Award and Carl Smith Medal from the University of Otago in 2020. Her group’s work is supported by grants from the Health Research Council of New Zealand, Cure Kids, Neurological Foundation of New Zealand (including support from the Broad Family Trust), University of Otago and the Marsden Fund.
Seminar: Mutations in Histone H4 underlie a novel neurodevelopmental disorder
Histones are well-studied for their developmental role in chromatin remodelling via dynamic and complex alterations to post-translational modifications, and many chromatin remodelers are associated with genetic disorders. In contrast, the core role of histones as part of the nucleosome is often ignored. We have recently identified a large cohort of individuals with mutations affecting the core domain of histone H4, all of whom have a neurodevelopmental disorder of intellectual disability and reduced brain size. In this seminar I will present our newly published findings, sharing the complex world of histone genomics, and the broader implications of genetic variation in histone genes.
Dr Giacomo Cavalli
Principles and functional role of 3D genome folding
Dr Giacomo Cavalli studied biology at the University of Parma, Italy. In 1991, he moved to Zürich to do his PhD at the University of Science and Technology (ETH), where he worked on chromatin structure and function in yeast with Fritz Thoma and Theo Koller.
In 1995, Giacomo began a postdoc in the laboratory of Prof Renato Paro, at the University of Heidelberg in Germany. In 1999, he moved to the Institute of Human Genetics (IGH) in Montpellier, France, to set up a junior lab, and he has stayed at IGH ever since.
Giacomo has made seminal contributions in the field of epigenetics. Using the fruit fly Drosophila melanogaster, he discovered that epigenetic inheritance of new phenotypes can occur independently on changes of the DNA sequence. His lab also discovered that the three-dimensional organisation of chromosomes in the cell nucleus is a heritable trait that plays an important gene regulatory role. The Cavalli lab identified 3D structural chromosomal domains dubbed Topologically Associating Domains or TADs. Finally, the Cavalli lab has shown that PcG proteins have tumor suppression activity in flies.
Giacomo Cavalli has published more than 120 papers, cited over 16,000 times and many of which in top journals. He has received numerous awards and distinctions, including an EMBO membership, the CNRS silver medal, the Allianz Foundation price, the Grand Prix 2020 of the Fondation pour la Recherche Médicale and two advanced ERC grants. He was director of the IGH Genome Dynamics department from 2007 to 2010 and IGH director from 2011 to 2014. He was and is organizer of major international conferences and is appointed as members of several distinguished Institute- and Journal editorial boards.
Seminar: Principles and functional role of 3D genome folding
The eukaryotic genome folds in 3D in a hierarchy of structures, including nucleosomes, chromatin fibers, loops, chromosomal domains (also called TADs), compartments and chromosome territories that are highly organized in order to allow for stable memory as well as for regulatory plasticity, depending on intrinsic and environmental cues. Our lab has provided evidence suggesting that the formation of TADs and chromatin loops can assist gene regulation, both in Drosophila and in mouse cells. Furthermore, cellular stress, such as replicative or oncogene-induced senescence, can induce a massive nuclear reorganization that can affect gene expression. However, the physical nature of compartments, TADs and loops remain elusive and single-cell studies are critically required to understand it.
We characterized chromatin folding in single cells using super-resolution microscopy, revealing structural features inaccessible to cell-population analysis. TADs range from condensed and globular objects to stretched conformations. Favored interactions within TADs are regulated by cohesin and CTCF through distinct mechanisms. Furthermore, super-resolution imaging revealed that TADs are subdivided into discrete nanodomains.
We also analyzed loops that depend on chromatin components that regulate the expression of a large number of genes, dubbed as Polycomb group proteins. Originally, these factors were shown to silence gene expression and we found that they induce the formation of chromatin loops. The disruption of one of these loops reduces silencing of a target genes, suggesting that loops may play instructive roles in gene regulation. Surprisingly, Polycomb components are also involves in chromatin loops linked with transcriptional activation.
Our progress in these fields will be discussed.
Prof Julia Horsfield
How signalling pathways interact with cohesin deficiency
Julia Horsfield graduated with a PhD in Biochemistry from the University of Otago in 1995, and did her postdoctoral research at the University of Adelaide 1996-1999. In a second postdoctoral stint as a Research Fellow at the University of Auckland, she was the first to discover a gene regulation role for cohesin in a vertebrate model – the zebrafish.
Since 2007, Julia has led the Chromosome Structure and Development Group at the University of Otago. The overall goal of the group’s research is to understand chromatin mechanisms contributing to gene expression in development and cancer, using mammalian cancer cell lines, induced pluripotent stem cells, and of course, the zebrafish.
Seminar: How signalling pathways interact with cohesin deficiency
The cohesin complex plays key roles in the three-dimensional (3D) organisation of chromatin and is essential for cell division and gene expression. Cohesin’s role in 3D genome organisation helps determine the accessibility of genes to transcriptional programmes downstream of signalling pathways. We and others have found that hundreds of genes are dysregulated upon cohesin deficiency, but it is not clear how this gene regulation could be ‘direct’. Our results show that minor gene expression changes in cohesin-deficient cells become dramatic in response to signalling pathways. Cohesin deficiency causes loss of constraints on 3D structure such that genes respond abnormally, transiently, when a signal is present, with dependence on enhancer function. Unconstrained 3D chromatin structure may not be the whole picture, because we recently found that the Wnt effector protein, beta-catenin, is stabilised in cohesin mutant cells. This raises the possibility that signalling pathways and cohesin mutation compound to abnormally regulate gene expression at multiple levels. Overall, these results have relevance to the interpretation of “cohesinopathy” human developmental syndromes, and a range of cancers, that are caused by mutations in the cohesin complex or its regulators.
Dr Shom Goel
Therapy-induced senescence in cancer
Dr Shom Goel is a clinician-scientist at the Peter MacCallum Cancer Centre in Melbourne.
Shom returned to Australia in 2019, having spent ten years in Boston where he completed his doctoral and postdoctoral research. Shom’s research group positions itself at the intersection of cell cycle biology, epigenetics and tumour immunology in breast cancer. They have developed several new transgenic mouse models of breast cancer, which have proven valuable for uncovering new mechanisms of drug activity and resistance, and their work has been published in high-impact journals including Nature, Cancer Cell and Nature Cancer.
Shom serves as either Global PI or Translational PI for four randomised clinical trials in Breast Cancer, and was recently appointed Chair-Elect of the American Society of Clinical Oncology Education Committee.
Read more in our Spotlight on: Shom Goel.
Dr Lisa Marie Nicholas
Developmental programming of diabetes by maternal obesity – understanding the role of DNA methylation in pancreatic islets
Dr Lisa Marie Nicholas is an NHMRC C J Martin Fellow and leads the Epigenetics in Diabetes Research Group at the University of Adelaide. Lisa undertook her doctoral studies at the University of South Australia followed by post-doctoral training at Lund University Diabetes Centre where she investigated the role of mitochondria in maintaining pancreatic beta-cell function. Lisa then moved to the University of Cambridge where she defined early functional changes in the pancreatic islets of offspring exposed to maternal obesity leading to sex-specific differences in diabetes risk in later life.
Lisa continues to be fascinated by how a how a child’s metabolic destiny is determined even before birth by their mother’s metabolic health during pregnancy. Specifically, research in her group aims to discover the epigenetic networks in pancreatic beta-cells driving increased type 2 diabetes risk in offspring exposed to maternal obesity using mouse models and primary human islets.
Seminar: Developmental programming of diabetes by maternal obesity – understanding the role of DNA methylation in pancreatic islets
The rapid rise in diabetes incidence over the past decades has highlighted the role of epigenetics (in addition to genetics) in contributing to disease risk. This includes aberrant epigenetic changes resulting from in utero exposure to poor maternal nutritional states. Lisa will discuss whether DNA methylation has a role to play in mediating diabetes risk in offspring exposed to maternal obesity.
A/Prof Timothy Bredy
Research in the A/Prof Tim Bredy’s laboratory is aimed at elucidating how the genome is connected to the environment through epigenetic modifications, and how this relationship shapes brain and behaviour throughout life. Tim and his group are particularly interested in how epigenetic mechanisms, including DNA methylation, histone modifications, the activity of non-coding RNAs, and RNA modifications regulate the formation and maintenance of associative fear-related memory.
Read more in our Spotlight on: Tim Bredy.
A/Prof Luke Selth
Post-transcriptional regulation of prostate cancer cell plasticity
Associate Professor Luke Selth is head of the Prostate Cancer Research Group at Flinders University, South Australia, and a Beat Cancer Principal Research Fellow.
Research in the Selth Lab aims to elucidate how prostate tumours metastasise and become resistant to therapies, with a particular focus on non-genomic mechanisms. Luke and his group feed this newly gained knowledge into translational research projects aimed at developing new drugs and biomarkers to improve patient outcomes.
To achieve these research aims, the Selth lab exploits a unique assortment of model systems (including contemporary patient-derived models) and cutting-edge omic techniques.
The Selth lab is currently funded by Cancer Council SA, Movember, The Hospital Research Foundation, the Flinders Foundation and Cancer Australia.
Post-transcriptional regulation of prostate cancer cell plasticity
Targeted therapies in prostate cancer can cause epithelial tumours to switch to a neuroendocrine phenotype, a resistance mechanism that is mediated primarily by non-genomic alterations. In this presentation, Luke will describe recent work from his lab in which they have characterised novel post-transcriptional mechanisms underlying epithelial-neuroendocrine plasticity and therapy resistance.
A/Prof Ozren Bogdanovic
Canonical and non-canonical DNA methylation remodelling during early embryogenesis
Associate Professor Ozren Bogdanovic completed his undergrad studies at the University of Zagreb (Croatia) and his PhD at the Radboud University Nijmegen (the Netherlands). Upon the completion of his postdoctoral studies at the Andalusian Centre for Developmental Biology (Spain) and UWA (Perth), he started the Developmental Epigenomics Lab at the Garvan Institute of Medical Research in Sydney in 2017.
Since 2019, Ozren has held a joint position between Garvan and UNSW (School of BABS). His lab investigates the contribution of epigenetic mechanisms to embryogenesis, germline formation, and disease. The Developmental Epigenomics Lab employs teleost systems, CRISPR/Cas9 genome editing and genomics to study the developmental dynamics of epigenetic marks such as DNA methylation and histone modifications.
Canonical and non-canonical DNA methylation remodelling during early embryogenesis.
Early development is characterised by extensive DNA methylome reprogramming events; however, their exact function, biochemical mechanisms and evolutionary conservation remain enigmatic. In this seminar, Ozren will discuss how canonical (CG) and non-canonical (non-CG) methylation are reprogrammed during the earliest stages of teleost development, and the implications these have for our understanding of comparable events in mammals.
Prof Wendy Bickmore
MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, UK
The role of spatial proximity in genome regulation
Professor Wendy Bickmore is Director of the MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine at the University of Edinburgh, UK.
Wendy is fascinated by the structure and organization of chromatin in the nucleus. Her group showed that different human chromosomes have preferred positions in the nucleus, related to their gene content, and addressed how genes are organized and packaged in the nucleus and how they move in the cell cycle and during development. She demonstrated that the polycomb repressive complex functions by compacting higher-order chromatin at target loci.
Current research in Wendy Bickmore’s laboratory focuses on how the spatial organization of the nucleus influences genome function in development and disease, including how distant enhancers communicate with their target gene promoters.
Wendy is an EMBO member, a Fellow of the Royal Society and of the Academy of Medical Sciences. She is an editor on many journals including PLoS Genetics and Cell. She was the president of the Genetics Society of Great Britain from 2015 to 2018 and was awarded a CBE in the 2021 New Year Honours List for services to biomedical science and for women in Science.
Professor Margreet Vissers
Department of Pathology and Biomedical Science, University of Otago
Identifying effects of variable dietary vitamin C intake on the activity of the TET demethylases in vivo
Professor Greg Jones
Department of Surgical Sciences (Dunedin), University of Otago
Dr Tanya Soboleva
The John Curtin School of Medical Research, Australian National University
Identifying new regulators of cancer: the role of cancer-testis genes
Dr Tatiana (Tanya) Soboleva is a fellow at the Genome Biology Department in the John Curtin School of Medical Research, Australian National University.
Tanya graduated as a biochemist from Moscow State University in 1998 and moved to Australia after receiving a highly competitive International Postgraduate Research Scholarship, to study nucleocytoplasmic transport of deubiquitinating enzymes with Dr Baker.
After graduation in 2003, Tanya moved into the field of cytokine biology under the mentorship of Prof Young. In 2006, she joined Prof Tremethick’s laboratory at the ANU, where she discovered a novel histone variant, H2A.B3.
In 2019 Tanya established an independent research team to study epigenetic mechanisms by which histone variants control male germ cell differentiation and, in parallel, their involvement in carcinogenesis.
Tanya is a recognised expert in the field of epigenetics of spermatogenesis.
Professor Peter Jones
Van Andel Institute, USA
The whys and hows of DNA methylation
Professor Peter Jones was born in Cape Town, raised and attended college in Rhodesia (now Zimbabwe), and received his Ph.D. from the University of London. He joined the University of Southern California in 1977 and served as Director of the USC Norris Comprehensive Cancer Center between 1993 and 2011. Peter became Chief Scientific Officer of Van Andel Institute (VAI) in Grand Rapids, Michigan in 2014.
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.
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.