Active Motif's Podcast

In this episode of the Epigenetics Podcast, we caught up with Dr. Chuan He, John T. Wilson Distinguished Service Professor at University of Chicago, to talk about his work on the influence of dynamic RNA methylation on gene expression. RNA methylation is an important biological process, and cellular RNA methylation levels can have profound impacts on normal cellular differentiation and cancer cell proliferation. Dr. He received his Ph.D. from MIT in 2000 and went on to do his postdoctoral work at Harvard University. He then became Assistant Professor at the University of Chicago in 2002, was promoted to Associate Professor in 2008, and in 2014 he became the John T. Wilson Distinguished Service Professor at the University of Chicago.  From 2012 to 2017 he was Director of the Institute for Biophysical Dynamics at the University of Chicago. Chuan He's current research focuses on understanding the reversible RNA modification m6A. This modification was discovered in the 1980s, but work from Dr. He's laboratory s

In this episode of the Epigenetics Podcast, we caught up with Dr. Michelle Trenkmann, Senior Editor at Nature. We discussed her work as an editor at Nature and how she contributed to the ENCODE 3 publications, which are the results of the third phase of the ENCODE project. Dr. Trenkmann also talked about how to get your research published in Nature and what it’s like to review high profile scientific articles.   ENCODE References   Immersive ENCODE Website Perspectives on ENCODE   Contact   Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on Linked-In Active Motif on Facebook eMail: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Professor Bill Earnshaw, Wellcome Trust Principal Research Fellow at the University of Edinburgh, to talk about his work on the role of non-histone proteins in chromosome structure and function during mitosis.   In the beginning of Bill Earnshaw's research career little was known about the structure that holds the two individual sister chromatids together. This led to Bill pioneering in the use of autoantibodies for the identification and cloning of key chromosomal proteins. He used serum from a scleroderma patient to identify and clone human centromeric proteins, which paved the way for the molecular characterization of the metazoan kinetochore.   Later the chromosomal passenger complex (CPC) was identifies in his lab using biochemical studies. This complex contains Aurora B kinase plus its targeting and regulatory subunits INCENP, Survivin, and Borealin/Dasra B.    More recently, he teamed up with the laboratories of Job Dekker and Leonid M

In this episode of the Epigenetics Podcast, we caught up with Dr. Dirk Schübeler, Director of the Friedrich Miescher Institute (FMI) in Basel, Switzerland, to talk about his work on the effects of DNA methylation on chromatin structure and transcription.   Dirk Schübeler was born in Germany and started his scientific career in Braunschweig, Germany. After his postdoc at the Fred Hutchinson Cancer Research Center in Seattle, he joined the FMI in 2003 and never left. He was recently appointed as the Director of the FMI in March 2020.   Dirk Schübeler’s research focuses on DNA methylation and its effects on chromatin and transcription. It is widely known that DNA methylation leads to gene silencing, but many of the mechanisms and regulatory factors involved in this process remain understudied. Therefore, Dirk Schübeler and his team set out to characterize the DNA methylation profiles in normal human somatic cells and compare them with the methylation profiles in transformed human cells. More recent work in h

In this episode of the Epigenetics Podcast, we caught up with Sir Adrian Bird, Buchanan Professor of Genetics at the University of Edinburgh to talk about his work on CpG islands, DNA methylation, and the role of DNA methylation in human diseases.   Adrian Bird has been a pioneer in studying the CpG dinucleotide sequence. The CpG dinucleotide is distributed genome-wide and has several properties expected of a genomic signaling module. The influence of CpG signaling on prozesses like development, differentiation, and disease is hardly understood. Adrian Bird's work indicates that proteins that bind methylated CpGs recruit chromatin modifying enzymes to promote gene silencing. On the other hand, proteins that bind unmethylated CpGs lead to the formation of active, open chromatin. These results suggest that CpGs have a gobal effect on genome activity.   In neurons MeCP2 is almost as abundant as histones and is probably one of the best studied Proteins that bind to methyl-CpGs. Children who lack MeCP2 acquire

In this episode of the Epigenetics Podcast, we caught up with Leonid Mirny, Ph.D., from MIT to talk about his work on biophysical modeling of the 3-D structure of chromatin. Leonid Mirny was part of the initial Hi-C paper titled "Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome" that was published in 2009 in the journal Science. Since then, technology has evolved and Dr. Mirny's group has developed a method called Micro-C that improves the Hi-C protocol by using MNase digestion to increase the resolution to nucleosomal level. This led to the visualization of interactions that were already predicted by his previous biophysical models. Furthermore, Leonid Mirny worked on finding the mechanism by which chromatin loops are formed. He and his team proposed that loop extrusion underlies TAD formation. In this process, factors like cohesin and CTCF form progressively larger loops but stall at TAD boundaries due to interactions of CTCF with TAD boundaries. He used poly

In this episode of the Epigenetics Podcast, we caught up with Karolin Luger, Ph.D., from the University of Colorado in Boulder to talk about her work on solving the crystal structure of the nucleosome and on how histone chaperones like FACT act on chromatin. During her postdoc with Timothy Richmond at the Swiss Federal Institute of Technology in Zürich, Karolin Luger was the first author on an all-time classic paper called "Crystal structure of the nucleosome core particle at 2.8 A resolution" which was published in Nature. This article was published more than 20 years ago now and it has been cited about 9000 times. After completing her postdoc, she moved to Colorado to set up her own lab where she continued to work on the structure of the nucleosome and the factors that influence their structure. The most recent Nature paper published by her lab investigated how the FACT complex promotes both disassembly and reassembly of nucleosomes during gene transcription, DNA replication, and DNA repair.   In this in

In this episode of the Epigenetics Podcast, we caught up with Bing Ren, Ph.D., from the University of California, San Diego and the Ludwig Institute for Cancer Research to talk about his work on identifying functional elements of the genome and higher order genome structure.   Dr. Ren’s lab invented an approach using chromatin immunoprecipitation-based methods for the identification of transcription factor binding sites and chromatin modification status genome-wide. His group  was a major part of the ENCODE Project and the demonstration of this being an effective method for genome-wide mapping of cis-elements, has made their approach very popular among colleagues from the field.   His lab recently discovered Topologically associating domains (TADs), which partition the human genome into a few thousand megabase-sized domains. Interactions occur predominantly within TADs but seldom between them and are surprisingly stable during development and are evolutionarily conserved. This organisatorial pattern helps

In this episode of the Epigenetics Podcast, we caught up with Erez Lieberman Aiden, Ph.D. from Baylor College of Medicine and Rice University in Houston to talk about his work on developing Hi-C and investigating the three-dimensional structure of the genome. He was the first author on a publication in the journal Science titled "Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome" which was the paper that first introduced the Hi-C method in 2009 and he has continued studying the structure of the chromosome ever since. Erez Lieberman Aiden is currently an Assistant Professor in both the Department of Genetics at the Baylor College of Medicine, where he directs the newly-established Center for Genome Architecture, and in the Department of Computer Science and Computational and Applied Mathematics at Rice University across the street. In this interview, we discuss the road that Erez Lieberman Aiden went down to optimize the Hi-C protocol, the hurdles he had to over

In this episode of the Epigenetics Podcast, we caught up with Professor Tom Moss from Université Laval in Québec City, Canada to talk about his work on the chromatin structure and dynamics at ribosomal RNA genes. Dr. Tom Moss has been a member of the Department of Molecular Biology, Medical Biochemistry, and Pathology at the Laval University School of Medicine since he was recruited from the University of Portsmouth in the United Kingdom in 1986. Since then he focused on the ribosomal transcription factor Upstream Binding Factor (UBF) and how it regulates the chromatin structure at ribosomal RNA genes (rDNA). UBF binds to the rDNA as a dimer where it leads to six in-phase bends and induces the formation of the ribosomal enhanceosome. This enhanceosome is required for the initial step in formation of an RNA polymerase I initiation complex, and therefore plays an important role in regulating the expression of ribosomal RNA genes. In this Interview, we discuss the function of UBF on the rDNA, how UBF impacts

In this episode of the Epigenetics Podcast, we caught up with Dr. Andrew Pospisilik from the Van Andel Institute in Grand Rapids, Michigan to talk about his work on the epigenetic origins of heterogeneity and disease. Dr. Andrew Pospisilik worked at the Max-Planck Institute of Immunobiology and Epigenetics in Freiburg for 8 years and in 2018 he joined the Van Andel Institute as the director of its Center for Epigenetics. At the Van Andel Institute his research focuses on diabetes, neurodegenerative diseases, cancer, and obesity. The goal of the Pospisilik laboratory is to better understand epigenetic mechanisms of these diseases and the roles of epigenetics in disease susceptibility and heterogeneity.   These areas of medicine are among the most important public health challenges, with the latest estimates suggesting that they impact more than 1 billion people worldwide. Although these diverse conditions are all very different, they are now thought to be caused, at least partially, from alterations in the

In this episode of the Epigenetics Podcast, we caught up with Karol Bomsztyk M.D. and Tom Matula, Ph.D. from the University of Washington and Matchstick Technologies, to talk about their work on DNA and chromatin sonication. During his career, Karol's research has focused on improving ChIP protocols to make them faster, easier and higher throughput. First, to make ChIP assays faster, Karol and his lab developed "Fast-ChIP". More recently, he adjusted this protocol to improve throughput and "Matrix-ChIP" was born. Tom is an expert in the field of ultrasound and cavitation and the Director of the Center for Industrial and Medical Ultrasound at the University of Washington. To further improve and speed up the 96-well "Matrix-ChIP" protocol, Karol and Tom teamed up to found Matchstick Technologies and develop a sonication device that would be able to processes each and every well of a 96-well microplate consistently and quickly. The result of this cooperation is the PIXUL Multi-Sample Sonicator that is now avai

In this episode of the Epigenetics Podcast, we sat down with Marcus Buschbeck, Group Leader at the Josep Carreras Leukaemia Research Institute in Barcelona, to talk about his work on the histone variant macroH2A, its role in metabolism and how it contributes to the regulation of chromatin structure.   Histone variants equip chromatin with unique properties and show a specific genomic distribution. The histone variant macroH2A is unique in having a tripartite structure consisting of a N-terminal histone-fold, an intrinsically unstructured linker domain and a C-terminal macro domain. Recent discoveries show that macroH2A proteins have a major role in the nuclear organization which has the potential to explain how these proteins can act as tumor suppressors, promoters of differentiation and barriers to somatic cell reprogramming.   We discuss these topics, the mission of the Josep Carreras Leukaemia Research Institute, and much more in this episode.    References http://www.carrerasresearch.org/Buschbeck_

In this Episode we sat down with Shelley Berger, Keynote Speaker at the "EMBO | EMBL Symposium: Metabolism Meets Epigenetics" to talk about her work on Epigenetic Mechanisms of Aging and Longevity. On how cytoplasmic chromatin fragments are involved in these processes, how alcohol has an effect on Histone PTMs in the brain and last but not least how Ants became her favorite Model Organism. References Hazel A. Cruickshanks, Tony McBryan, … Peter D. Adams (2013) Senescent cells harbour features of the cancer epigenome (Nature Cell Biology) DOI: 10.1038/ncb2879 Zhixun Dou, Kanad Ghosh, … Shelley L. Berger (2017) Cytoplasmic chromatin triggers inflammation in senescence and cancer (Nature) DOI: 10.1038/nature24050  Hua Yan, Comzit Opachaloemphan, … Claude Desplan (2017) An Engineered orco Mutation Produces Aberrant Social Behavior and Defective Neural Development in Ants (Cell) DOI: 10.1016/j.cell.2017.06.051  P. Mews, G. Egervari, … S. L. Berger (2019) Alcohol metabolism contributes to brain histone acetyl

In this Episode of the Epigenetics Podcast our guest Lucy Stead from the University of Leeds provides insight into her work on intratumor heterogeneity in Glioblastoma. In order to tackle this area she uses an holistic approach including Computational Genomics, In silico Modeling and Functional Genomics in order to test whether treatment-resistant subclones emerge in recurrent tumors, and characterize them in clinically relevant ways in multiple patients. And this is just a glimpse of what is discussed in this Episode.   References  Lucy F. Stead, Helene Thygesen, … Pamela Rabbitts (2015) Using common variants to indicate cancer genes (International Journal of Cancer) DOI: 10.1002/ijc.28951  Caroline Conway, Jennifer L. Graham, … Lucy F. Stead (2015) Elucidating drivers of oral epithelial dysplasia formation and malignant transformation to cancer using RNAseq (Oncotarget) DOI: 10.18632/oncotarget.5529  Alastair Droop, Alexander Bruns, … Lucy F. Stead (2018) How to analyse the spatiotemporal tumour sample

Joe Fernandez, the founder of Active Motif, has played a significant role in the evolution of the biotechnology industry. He’s seen where the industry has been, and he has a good idea where it’s going.  Prior to founding Active Motif in 1999, Joe was a co-founder of Invitrogen where he helped revolutionize molecular cloning with the TOPO TA kit. Joe’s passion for disrupting established workflows by making them easier and more efficient didn’t stop there. With Active Motif, he launched the first ever ChIP kit in 2003, and the company now offers the most complete portfolio of ChIP kits for different workflows and sample types, the highest quality ChIP-validated antibodies, and the most comprehensive and most cited end-to-end Epigenetic Services.  In this interview, we sat down with Joe to learn how he got started in science, what he’s currently excited about, and what he thinks will be the next big thing in epigenetics research.     Contact   https://twitter.com/activemotif https://twitter.com/epigenetic

In this Episode of the Epigenetics Podcast our guest Ana Pombo from the Max-Delbrück-Center in Berlin provides insight in her work on the interplay between gene regulation and genome architecture. To do so she and her team use different state of the art methods, including cryo-sectioning to unravel this regulatory network. In 2006, they proposed the Interchromatin Network Model of chromosome organization which postulates that chromosome folding is driven by contacts between different genomic regions and between chromatin and nuclear landmarks, such as the nuclear lamina. And later on they used polymer physics modeling to study those mechanisms, which lead to the development of the Strings & Binders Switch (SBS) model. And this is just a glimpse of the topics that are discussed in this Episode.   References Miguel R. Branco, Ana Pombo (2006) Intermingling of Chromosome Territories in Interphase Suggests Role in Translocations and Transcription-Dependent Associations (PLOS Biology) DOI: 10.1371/journal.pb

Dosage compensation is an essential process to regulate the gene expression of the X-chromosome in female and male flies. Thereby the mechanism of regulation in humans and in drosophila is different. In humans one X-chromosome is randomly shut down in females compared to men, whereas in drosophila equilibrium is achieved by overexpression of the single X-chromosome in males. In this Episode our guest Dr. Asifa Akhtar provides information on her work on dosage compensation in drosophila melanogaster and how the MSL-complex, the Histone-acetyltransferase MOF work together in this process. Furthermore, she also talks about potential functions of those Proteins in the human system.   References  Jan Kadlec, Erinc Hallacli, … Asifa Akhtar (2011) Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1 (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.1960  Thomas Conrad, Florence M.G. Cavalli, … Asifa Akhtar (2012) The MOF Chromobarrel Domain Controls Genome-wide H

In recent years it has become more and more evident, that genome folding and chromatin packaging into the nucleus plays a pivotal role in the regulation of gene expression. In this Episode of our Podcast our host Dr. Stefan Dillinger spoke with Professor Wendy Bickmore about her work on the spatial organization of the human genome. Prof. Bickmore and her team mainly use visual methods like fluorescence in situ hybridisation (FISH) to study the organization of chromosomes in human and murine cells and how they contribute to transcriptional regulation and how this organization changes during ageing, development or disease. References Charlene Boumendil, Priya Hari, … Wendy A. Bickmore (2019) Nuclear pore density controls heterochromatin reorganization during senescence (Genes & Development) DOI: 10.1101/gad.321117.118  Charlene Lemaître, Wendy A. Bickmore (2015) Chromatin at the nuclear periphery and the regulation of genome functions (Histochemistry and Cell Biology) DOI: 10.1007/s00418-015-1346-y  Ja

Heterochromatin plays a pivotal role in organizing our genome in the nucleus and separating active from inactive genomic regions. In this Podcast Episode our Guest Gary Karpen from UC Berkeley sits down with our Host Stefan Dillinger to talk about the regulation of this chromatin structure and how DNA repair mechanisms function in this densely packed nuclear compartment. Furthermore, they also discuss how phase separation might be an important part in how heterochromatin domains are formed. References Jamy C. Peng, Gary H. Karpen (2009) Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation (PLoS Genetics) DOI: 10.1371/journal.pgen.1000435 Peter V. Kharchenko, Artyom A. Alekseyenko, … Peter J. Park (2011) Comprehensive analysis of the chromatin landscape in Drosophila melanogaster (Nature) DOI: 10.1038/nature09725 Aniek Janssen, Serafin U. Colmenares, … Gary H. Karpen (2019) Timely double-strand break repair and pathway choice in pericentromeric heterochromatin depend on the hi