Online Epigenetics Seminar Series

Epigenetics Seminar Series 2022

We’re delighted to resume our online  Epigenetics Seminar Series in March 2022. A wonderful program has been planned, with the seminar hosted by one of our Committee members and featuring with a line-up of speakers from around Australia and overseas.

The Seminars will be held monthly (on alternate Tuesdays and Thursdays). 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.

Gold sponsor

Silver sponsors

Bronze sponsors

The Seminars will be held monthly (on alternate Tuesdays and Thursdays). 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.

Thurs 18 Aug 2022

12 – 1 pm (AEST) 

Host: Prof Ryan Lister

Prof Ian Campbell

Peter MacCallum Cancer Centre
Resolving the role of inherited promoter hypermethylation in hereditary breast cancer

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Professor Ian Campbell is Head of the Cancer Genetics Laboratory at the Peter MacCallum Cancer Centre and Professor in the Sir Peter MacCallum Department of Oncology at the University of Melbourne, Australia.

A major component of Ian’s research is the discovery of new familial breast and ovarian cancer predisposition genes through large scale sequencing approaches. He leads translational studies into mainstreaming germline and genetic sequencing for all women newly diagnosed with breast cancer and the development of a blood DNA based genetic test for quantitating future cancer risk.

Ian has made significant contributions to the understanding of the aetiology of ovarian cancer and continues to lead studies of the somatic molecular landscape of breast and ovarian cancer precursor lesions. He is also the lead investigator of Lifepool, which is a cohort of women attending Breast Screening services (lifepool.org) that combines health and lifestyle information, mammographic density data, genetic data and health linkage data from over 55,000 women.

About this seminar:

Resolving the role of inherited promoter hypermethylation in hereditary breast cancer

Background: Pathogenic coding region mutations in BRCA1, BRCA2 and PALB2 are major contributors to hereditary breast cancer (HBC) but collectively explain less than a quarter of the families tested in clinical practice. In contrast to the intensive, but largely unsuccessful, international efforts aimed at discovering new HBC genes, little attention has been given to the possibility that many of these families are explained by known HBC genes which are inactivated via alternative mechanisms. We hypothesised that a clinically important component of the uncovered inherited risk of breast cancer is due to inherited promoter hypermethylation. Constitutional promoter hypermethylation of specific genes in hereditary cancer syndromes has been reported, such as the MLH1 gene in a proportion of Lynch syndrome patients but whether the same mechanism explains some HBC families is largely unexplored. We utilised next generation sequencing approaches to interrogate the entire protomer regions of all HBC genes in germline DNA from a large cohort of women who have a very strong breast cancer family history but where all known genetic causes have been excluded.

Methods: Peripheral blood lymphocyte derived DNA from 600 index cases of breast/ovarian cancer families from the BEACCON study (npj Breast Cancer 2021, 7:78) with no clinically detectable exonic or essential splice site mutations in known HBC genes were included in the study.  Many cases were carriers of rare 5′ UTR variants.  The average Manchester score of the cases was 26.9 (3-60) with 74 having scores >34. Also included were two cases previously reported to show constitutional hemizygous promoter methylation in BRCA1 due to a rare 5′ UTR variant (Evans et al., Am J Hum Genet, 2018. 103:213-20). The entire promoter region of 16 genes (ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, PALB2, PTEN, PMS2, RAD51C, RAD51D, STK11, TP53) were sequenced using the Twist NGS Methylation Detection System. Data was analysed using Bismark bisulfite mapper software.

Results: Cytosine to thymine conversion was >99% for the majority of samples and methylation sequencing quality was very good with an average sequencing depth of 105x. Hemizygous BRCA1 promoter methylation was confirmed in the cases previously reported Evans et al. No constitutional methylation (50% methylation) was detected in any of the 16 genes in any of BEACCON cases including those with very high Manchester scores.

Conclusions: Constitutional hemizygous promoter hypermethylation of known HBC genes is very rare and not a significant contributor to hereditary breast cancer.

September 2022

No seminar this month due to Epigenetics 2022 meeting.

October 2022

12 – 1 pm (AEST) 

Host: Dr Adele Woodhouse

Dr Paul Marshall

Queensland Brain Institute

November 2022

12 – 1 pm (AEST) 

Host: Dr Tanya Soboleva

Dr Melanie Eckersley-Maslin

Peter MacCallum Cancer Centre

We extend many thanks to our generous sponsors this year:

Gold sponsor

Silver sponsors

Bronze sponsors

Past seminars:

Tues 19 July 2022

12 – 1 pm (AEST) 

Host: A/Prof Jason Lee

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Dr Jessamy Tiffen

Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney
Targeting BET proteins in melanoma: mechanisms and therapeutic opportunities

Dr Jessamy Tiffen leads the Melanoma Epigenetics Laboratory at the Centenary Institute. She has over ten years of experience in cancer cell and molecular biology research, and her current work focuses on how dysregulation of epigenetic modifiers can govern major hallmarks of melanoma, including initiation, progression, and resistance to treatment.

Jessamy completed her PhD in Cancer Genetics in 2011 at Sydney University with Professor John Rasko. She conducted post-doctoral training at the Sanger Institute in Cambridge under the guidance of Dr David Adams, where she became interested in the genetics of melanoma.

She has published in Nature Genetics, Cancer Research and JNCI and currently holds project grant funding from the Cancer Council of NSW. In 2022  she was awarded a Career Development Fellowship from the Cancer Institute of NSW.

 

Seminar: Targeting BET proteins in melanoma: mechanisms and therapeutic opportunities

Bromodomain and extra-terminal (BET) proteins are epigenetic readers that are linked with poor prognosis in melanoma patients. In the following talk I will summarise our work deciphering the growth suppressive mechanisms of BET inhibition in our preclinical melanoma models, in vitro and in vivo. I will describe how BET inhibitors can be combined with other targeted or immunotherapies to make safe and effective rational combinations to combat treatment-resistant melanoma.

Thurs 16 June 2022

12 – 1 pm (AEST) 

Host: Dr Dimitrios Cakouros

A/Prof Jason Lee

QIMR Berghofer Medical Research Institute, QLD
Targeting histone methyltransferases in cancer: multiple mechanisms

Associate Professor Jason Lee is a Team Head at QIMR Berghofer Medical Research Institute and an Adjunct A/Prof at the University of Queensland and the Queensland University of Technology.

Jason completed his doctorate degree at the University of Sydney on the study of growth factors in breast cancer. He then moved to Dana-Farber Cancer Institute, Harvard Medical School as a postdoctoral fellow for the study of nuclear receptors in breast cancer. Before joining QIMR Berghofer, Jason was a research fellow then an Associate Professor at Seoul National University. He came back to Australia as a QIMR Berghofer International Research Fellow in 2013 in Professor Frank Gannon’s laboratory. In 2018, he has established his own group (Epigenetics and Disease Laboratory) and focuses on various research areas including molecular epigenetics, hypoxic signalling and cancer metastasis.

Jason is one of AEpiA’s  Committee members, as State Representatives for QLD.

Seminar: Targeting histone methyltransferases in cancer: multiple mechanisms

It has become evident in recent years that alterations in genes encoding proteins that regulate epigenetic modifications are common in human cancers. Histone methyltransferases play a crucial role in the physiological maintenance of homeostasis, the adaptive response to environmental challenges, or as the mediators of biological effects of therapeutic drugs. Changes in the expression of histone methyltransferases drive tumor initiation, influence cellular proliferation, metastasis, immune evasion and drug resistance. Therefore, targeting these enzymes is increasingly being recognized as an attractive therapeutic strategy for cancer. The goal of my research is to determine the role histone methyltransferases play in the development of therapy-resistance in multiple cancer types and determine the efficacy of histone methyltransferase inhibitors in overcoming resistance. Although the use of histone methyltransferase inhibitors have been heavily focused on targeting haematological cancers, there is an unappreciated therapeutic opportunity in treating therapy-resistant solid cancers. Combining the use of potent and specific inhibitors of histone methyltransferases with relevant biomarkers may improve treatment response of cancer patients.

Thurs 19 May 2022

12 – 1 pm (AEST) 

Host: Dr Vicki Whitehall

A/Prof Luciano Martelotto

A brief overview of my favourite single cell and spatial epigenomics technologies

A/Prof Luciano Martelotto (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.

Thurs 21 April 2022

12 – 1 pm (AEDT) 

Host: Dr Melanie Eckersley-Maslin

 

Read more about Hamish in our Spotlight on: Hamish King

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. 

Tues 15 March 2022

12 – 1 pm (AEDT) 

Host: Dr Tim Hore

Read more about Louise in our Spotlight on: Louise Bicknell

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.

Tues 16 Nov 2021*

4 – 5 pm (AEDT) 

Host: Dr Heather Lee

*Note: Different day and time as overseas guest speaker

 

Read more about Giacomo in our Spotlight on: Giacomo Cavalli

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.

Thurs 21 Oct 2021

1 – 2 pm (AEST)

Host: Prof David Tremethick

Read more about Julia in our Spotlight on: Julia Horsfield

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.

Thurs 16 Sept 2021

1 – 2 pm (AEST) 

Host: A/Prof Adele Holloway

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.

Thurs 19 August 2021

1 – 2 pm (AEST)

Host: A/Prof Pilar Blancafort

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.

Thurs 15 July 2021

1 – 2 pm (AEST) 

Host: A/Prof Jason Lee

A/Prof Timothy Bredy

New insights into long noncoding RNAs in the brain

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.

Thurs 17 June 2021

1 – 2 pm (AEST) 

Host: Dr Tina Bianco-Miotto

A/Prof Luke Selth

Flinders University, South Australia

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.

Thurs 20 May 2021

1 – 2 pm (AEST)

Host: Dr Fatima Valdes Mora

A/Prof Ozren Bogdanovic

Laboratory Head Developmental Epigenomics Lab, Garvan Institute of Medical Research, NSW
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.

Thurs 15 April 2021

4 – 5 pm (AEDT)

Host: Prof Jeff Craig

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.

Thurs 18 March 2021

Host:

A/Prof Aniruddha Chatterjee

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

AND

 

Professor Greg Jones

Department of Surgical Sciences (Dunedin), University of Otago

Thurs 12 Nov 2020

Host: Prof David Tremethick

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.

Thurs 22 Oct 2020

Host: Dr Phillippa Taberlay

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.

Thurs 17 Sept 2020

12.00 – 12.45pm (AEST)

Host: Prof Ryan Lister

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.

Thurs 20 Aug 2020

12.00 – 12.45pm (AEST)

Host: A/Prof Vicki Whitehall

Professor Sudha Rao

QIMR Berghofer

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.

Thurs 23 July 2020

12.00 – 12.45pm

Host: A/Prof Bastien Llamas

Professor Jus St. John

The University of Adelaide

Genomic balance

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.

Thurs 25 June 2020

12.00 – 12.45pm (AEST)

Host: Dr Heather Lee

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.