Episodes
Episodes
Wednesday Feb 19, 2020
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
Wednesday Feb 19, 2020
Wednesday Feb 19, 2020
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 epigenetic mechanisms that regulate gene expression and metabolism. This interview covers recent work from the Pospisilik lab on the epigenetics of these complex diseases.
References
https://pospisiliklab.vai.org/
J. Andrew Pospisilik, Daniel Schramek, … Josef M. Penninger (2010) Drosophila Genome-wide Obesity Screen Reveals Hedgehog as a Determinant of Brown versus White Adipose Cell Fate (Cell) DOI: 10.1016/j.cell.2009.12.027
Anita Öst, Adelheid Lempradl, … J. Andrew Pospisilik (2014) Paternal diet defines offspring chromatin state and intergenerational obesity (Cell) DOI: 10.1016/j.cell.2014.11.005
Kevin Dalgaard, Kathrin Landgraf, … J. Andrew Pospisilik (2016) Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity (Cell) DOI: 10.1016/j.cell.2015.12.025
Tess Tsai-Hsiu Lu, Steffen Heyne, … J. Andrew Pospisilik (2018) The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes (Cell Metabolism) DOI: 10.1016/j.cmet.2018.04.013
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eMail: podcast@activemotif.com
Tuesday Jan 28, 2020
PIXUL: On the Leading Edge of Chromatin Shearing (Karol Bomsztyk and Tom Matula)
Tuesday Jan 28, 2020
Tuesday Jan 28, 2020
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 available for order from Active Motif.
PIXUL is an ultrasound-based sample preparation platform that was designed completely from the ground up to provide researchers with an easy-to-use tool that is simple to set up, simple to use, and generates consistent results day in and day out. No other sample preparation platform out there can match the power and convenience of PIXUL.
PIXUL was conceived by an epigenetics researcher, and designed and built by ultrasound engineers to take the guesswork out of sample preparation. With PIXUL, sample preparation is no longer an art form, but instead a simple and predictable part of experiments that work every single time.
This interview goes into the mechanism behind sonication-based shearing of DNA and chromatin and highlights how PIXUL is different from existing sonication instruments.
References
http://activemotif.com/PIXUL
Karol Bomsztyk
Tom Matula
Innovation Imperative: New Device Speeds Disease Biomarker Search
Contact
Active Motif on Twitter
Epigenetics Podcast on Twitter
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eMail: podcast@activemotif.com
Monday Dec 16, 2019
Monday Dec 16, 2019
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_Marcus
Marcus Buschbeck, Iris Uribesalgo, … Luciano Di Croce (2009) The histone variant macroH2A is an epigenetic regulator of key developmental genes (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.1665
Julien Douet, David Corujo, … Marcus Buschbeck (2017) MacroH2A histone variants maintain nuclear organization and heterochromatin architecture (Journal of Cell Science) DOI: 10.1242/jcs.199216
Melanija Posavec Marjanović, Sarah Hurtado-Bagès, … Marcus Buschbeck (2017) MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption (Nature Structural & Molecular Biology) DOI: 10.1038/nsmb.3481
Oriana Lo Re, Julien Douet, … Manlio Vinciguerra (2018) Histone variant macroH2A1 rewires carbohydrate and lipid metabolism of hepatocellular carcinoma cells towards cancer stem cells (Epigenetics) DOI: 10.1080/15592294.2018.1514239
Contact
https://twitter.com/activemotif
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podcast@activemotif.com
Thursday Nov 21, 2019
Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)
Thursday Nov 21, 2019
Thursday Nov 21, 2019
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 acetylation (Nature) DOI: 10.1038/s41586-019-1700-7
Karl M. Glastad, Riley J. Graham, … Shelley L. Berger (2019) Epigenetic Regulator CoREST Controls Social Behavior in Ants (Molecular Cell) DOI: 10.1016/j.molcel.2019.10.012
Contact
https://twitter.com/activemotif
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https://www.linkedin.com/company-beta/35651/
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podcast@activemotif.com
Tuesday Oct 15, 2019
Epigenetics & Glioblastoma: New Approaches to Treat Brain Cancer (Lucy Stead)
Tuesday Oct 15, 2019
Tuesday Oct 15, 2019
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 samples needed to investigate cancer evolution: A case study using paired primary and recurrent glioblastoma (International Journal of Cancer) DOI: 10.1002/ijc.31184
Georgette Tanner, David R. Westhead, … Lucy F. Stead (2019) Simulation of heterogeneous tumour genomes with HeteroGenesis and in silico whole exome sequencing (Bioinformatics (Oxford, England)) DOI: 10.1093/bioinformatics/bty1063
Nora Rippaus, Alexander F-Bruns, … Lucy F. Stead (2019) JARID2 facilitates transcriptional reprogramming in glioblastoma in response to standard treatment (bioRxiv) DOI: 10.1101/649400
Contact
https://twitter.com/activemotif
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eMail: podcast@activemotif.com
Thursday Sep 05, 2019
Thursday Sep 05, 2019
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/epigenetics_pod
https://www.linkedin.com/company-beta/35651/
https://www.facebook.com/ActiveMotifInc/
podcast@activemotif.com
Monday Aug 12, 2019
The Interchromatin Network Model (Ana Pombo)
Monday Aug 12, 2019
Monday Aug 12, 2019
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.pbio.0040138
Robert A. Beagrie, Ana Pombo (2016) Gene activation by metazoan enhancers: Diverse mechanisms stimulate distinct steps of transcription (BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology) DOI: 10.1002/bies.201600032
Emily Brookes, Inês de Santiago, … Ana Pombo (2012) Polycomb Associates Genome-wide with a Specific RNA Polymerase II Variant, and Regulates Metabolic Genes in ESCs (Cell Stem Cell) DOI: 10.1016/j.stem.2011.12.017
Mario Nicodemi, Ana Pombo (2014) Models of chromosome structure (Current Opinion in Cell Biology) DOI: 10.1016/j.ceb.2014.04.004 - Robert A. Beagrie, Antonio Scialdone, … Ana Pombo (2017) Complex multi-enhancer contacts captured by genome architecture mapping (Nature) DOI: 10.1038/nature21411
Contact
https://twitter.com/activemotif
https://twitter.com/epigenetics_pod
https://www.linkedin.com/company-beta/35651/
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eurotech@activemotif.com
Tuesday Jul 16, 2019
Dosage Compensation in Drosophila (Asifa Akhtar)
Tuesday Jul 16, 2019
Tuesday Jul 16, 2019
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 H4K16 Acetylation and Spreading of the MSL Complex (Developmental Cell) DOI: 10.1016/j.devcel.2011.12.016
Maria Samata, Asifa Akhtar (2018) Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs (Annual Review of Biochemistry) DOI: 10.1146/annurev-biochem-062917-011816
Bilal N. Sheikh, Sukanya Guhathakurta, Asifa Akhtar (2019) The non-specific lethal (NSL) complex at the crossroads of transcriptional control and cellular homeostasis (EMBO reports) DOI: 10.15252/embr.201847630
Kin Chung Lam, Ho-Ryun Chung, … Asifa Akhtar (2019) The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise (Genes & Development) DOI: 10.1101/gad.321489.118
Claudia Isabelle Keller Valsecchi, M. Felicia Basilicata, … Asifa Akhtar (2018) Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells (Nature Communications) DOI: 10.1038/s41467-018-05642-2
Contact
https://twitter.com/activemotif
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eurotech@activemotif.com