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Epigenetics Podcast

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Epigenetics Podcast
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  • The Discovery of Genomic Imprinting (Azim Surani)
    In this episode, Professor Asim Surani, shares how his extensive research has significantly advanced the understanding of how the mammalian germline is specified, the mechanisms governing epigenetic reprogramming, and the critical conditions that maintain genomic integrity during early development. The discussion, led by Dr. Stefan Dillinger, provides an overview of Surani's journey into biology, the evolution of his research interests, and the pivotal discoveries that have shaped the field of epigenetics. Dr. Surani discusses the groundbreaking experiment he co-conducted in 1984 that led to the discovery of genomic imprinting. Initially a student involved in in vitro fertilization at Cambridge, he became intrigued by the implications of parthenogenesis in mammals. Challenging the prevailing cytoplasmic theory of development, Surani and his collaborators demonstrated that normal mammalian development requires contributions from both parental genomes, leading to the introduction of the concept of genomic imprinting—a term Surani defended to describe the phenomenon that he and his team observed. Surani's research then evolved toward understanding the mechanisms of genomic imprinting, particularly the role of DNA methylation. Throughout the interview, he details specific experiments that elucidated how genes could exhibit imprinted expression depending on the parental lineage, highlighting the importance of epigenetic factors in gene regulation. The revelation that DNA methylation marks were responsible for imprinting solidified the connection between genetic information and epigenetic influence in development. The conversation dives deeper into the mechanisms involved in germline specification and epigenetic reprogramming. Surani explains his transition into studying mammalian germline development and the intricacies of primordial germ cell specification. Working with his team, he utilized single-cell approaches to investigate gene expression profiles specific to germ cells, identifying critical factors like PRDM1 and PRDM14 that repress somatic gene programs while initiating germline-specific pathways. This work underscored the complex interplay of genetic and epigenetic factors that govern the development of germ cells. Another focus of the interview is the comparison of epigenetic resetting between mouse and human germlines. Surani addresses key differences in the timing and mechanisms of epigenetic reprogramming in humans, particularly the involvement of specific factors such as SOX17, which emerged as a crucial player in human germline specification, contrary to his earlier expectations. The discussion also highlights the technical challenges researchers face when studying human embryos due to ethical constraints, driving innovation in model systems such as stem cells to explore germline development.   References Surani MA, Barton SC, Norris ML. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature. 1984 Apr 5-11;308(5959):548-50. doi: 10.1038/308548a0. PMID: 6709062. Surani MA, Barton SC, Norris ML. Nuclear transplantation in the mouse: heritable differences between parental genomes after activation of the embryonic genome. Cell. 1986 Apr 11;45(1):127-36. doi: 10.1016/0092-8674(86)90544-1. PMID: 3955655. Ohinata Y, Payer B, O'Carroll D, Ancelin K, Ono Y, Sano M, Barton SC, Obukhanych T, Nussenzweig M, Tarakhovsky A, Saitou M, Surani MA. Blimp1 is a critical determinant of the germ cell lineage in mice. Nature. 2005 Jul 14;436(7048):207-13. doi: 10.1038/nature03813. Epub 2005 Jun 5. PMID: 15937476. Hajkova P, Ancelin K, Waldmann T, Lacoste N, Lange UC, Cesari F, Lee C, Almouzni G, Schneider R, Surani MA. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature. 2008 Apr 17;452(7189):877-81. doi: 10.1038/nature06714. Epub 2008 Mar 19. PMID: 18354397; PMCID: PMC3847605.   Related Episodes Epigenetic Reprogramming During Mammalian Development (Wolf Reik) Epigenetic and Metabolic Regulation of Early Development (Jan Żylicz) Epigenetic Mechanisms in Genome Regulation and Developmental Programming (James Hackett) Epigenetic Mechanisms of Mammalian Germ Cell Development (Mitinori Saitou) Exploring DNA Methylation and TET Enzymes in Early Development (Petra Hajkova)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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  • Exploring DNA Methylation and TET Enzymes in Early Development (Petra Hajkova)
    In this episode of the Epigenetics Podcast, we talked with Petra Hajkova from the MRC Laboratory of Medical Sciences about her work on epigenetics research on mammalian development, highlighting DNA methylation, histone modifications, and TET enzymes, along with her journey in molecular genetics and future research on epigenetic maintenance. Dr. Hajkova's early work focused on DNA methylation and resulted in innovative collaboration that allowed her to develop bisulfide sequencing techniques. We discuss her transition to the UK, where she began working in Azim Surani's lab at the University of Cambridge. Dr. Hajkova describes the excitement of researching chromatin dynamics in the mouse germline, leading to significant findings published in Nature. Her story highlights the intense yet rewarding nature of postdoctoral research as she navigated the complexities of working with embryos for the first time. As her research progressed, Dr. Hajkova established her own lab at the MRC London Institute of Medical Sciences, where she became a professor in 2017. We delve into her investigations on the differences between embryonic stem cells and embryonic germ cells regarding their distinct developmental origins. Dr. Hajkova outlines the challenges she faced in understanding the mechanisms behind global DNA demethylation in germline cells and the role of hydroxymethylation during early development. The discussion further covers her exciting findings regarding the specific functions of TET enzymes and their regulatory roles in maintaining epigenetic states. We explore her recent research published in Nature, which provides insights into the transition from primordial germ cells to gonocytes, emphasizing the significance of various epigenetic mechanisms in germline development.   References Hajkova P, Ancelin K, Waldmann T, Lacoste N, Lange UC, Cesari F, Lee C, Almouzni G, Schneider R, Surani MA. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature. 2008 Apr 17;452(7189):877-81. doi: 10.1038/nature06714. Epub 2008 Mar 19. PMID: 18354397; PMCID: PMC3847605. Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MA. Genome-wide reprogramming in the mouse germ line entails the base excision repair pathway. Science. 2010 Jul 2;329(5987):78-82. doi: 10.1126/science.1187945. PMID: 20595612; PMCID: PMC3863715. Hill PWS, Leitch HG, Requena CE, Sun Z, Amouroux R, Roman-Trufero M, Borkowska M, Terragni J, Vaisvila R, Linnett S, Bagci H, Dharmalingham G, Haberle V, Lenhard B, Zheng Y, Pradhan S, Hajkova P. Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte. Nature. 2018 Mar 15;555(7696):392-396. doi: 10.1038/nature25964. Epub 2018 Mar 7. PMID: 29513657; PMCID: PMC5856367. Huang TC, Wang YF, Vazquez-Ferrer E, Theofel I, Requena CE, Hanna CW, Kelsey G, Hajkova P. Sex-specific chromatin remodelling safeguards transcription in germ cells. Nature. 2021 Dec;600(7890):737-742. doi: 10.1038/s41586-021-04208-5. Epub 2021 Dec 8. PMID: 34880491.   Related Episodes Epigenetic Mechanisms of Mammalian Germ Cell Development (Mitinori Saitou) Epigenetic Reprogramming During Mammalian Development (Wolf Reik) DNA Methylation and Mammalian Development (Déborah Bourc'his)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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  • Epigenetic Regulation and Small Molecule Innovation in AML: Advances in Translational Leukemia Research (Ani Deshpande)
    In this episode of the Epigenetics Podcast, we talked with Ani Deshpande from Sanford Burnham Prebys about his work on epigenetic regulation and developing small molecules through high throughput screens for AML. Throughout our discussion, we delve into Dr. Despande's journey into the field of biology and science, tracing his evolution from a literature enthusiast in Mumbai to a dedicated cancer researcher. He reflects on his formative experiences during his PhD at Ludwig Maximilian University in Munich, where she developed murine models for refractory acute myeloid leukemia (AML). We examine these models' contributions to therapeutic discovery and understanding the intricate mechanisms underscoring AML's complexities. Transitioning to his postdoctoral work at Scott Armstrong's lab in Boston, Dr. Despande shares his insights on the importance of epigenetic regulators, such as DOT1L, in leukemias, and how they can serve as strategic therapeutic targets. His ambitious pursuit of translational research is further highlighted through his efforts in developing a conditional knockout mouse model and his collaborative work utilizing CRISPR technology to refine our understanding of epigenetic regulation in cancer pathogenesis. Moreover, we engage in a conversation about the challenges and opportunities that arise when establishing his lab at Sanford Burnham Prebys. Dr. Despande candidly discusses the delicate balance between pursuing topics of genuine interest versus adhering to grant fundability, underlining the tension researchers face in the current scientific landscape. His emphasis on the critical need for innovation within lab settings serves as a motivational call for emerging scientists to venture beyond the established templates that often inhibit groundbreaking discoveries. We conclude our dialogue with an exploration of his recent projects, which involve targeting specific epigenetic modifiers and how his lab’s findings can contribute to greater understanding and potential treatments for not only AML but also other pediatric cancers driven by gene fusions. Dr. Despande's insights into the integration of modern technologies, such as CRISPR libraries, exemplify his commitment to pushing the boundaries of cancer research. In addition to discussing his scientific contributions, we touch upon Dr. Despande's foray into podcasting (The Discovery Dialogues), shedding light on his motivation to bridge the communication gap between scientists and the broader public. He articulates his desire to demystify scientific discoveries and promote awareness about the intricate journey of research that lays the groundwork for medical advancements. This multidimensional discussion not only highlights his scientific achievements but also emphasizes the importance of effective science communication in fostering public understanding and appreciation of research.   References Deshpande AJ, Cusan M, Rawat VP, Reuter H, Krause A, Pott C, Quintanilla-Martinez L, Kakadia P, Kuchenbauer F, Ahmed F, Delabesse E, Hahn M, Lichter P, Kneba M, Hiddemann W, Macintyre E, Mecucci C, Ludwig WD, Humphries RK, Bohlander SK, Feuring-Buske M, Buske C. Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia. Cancer Cell. 2006 Nov;10(5):363-74. doi: 10.1016/j.ccr.2006.08.023. PMID: 17097559. Deshpande AJ, Deshpande A, Sinha AU, Chen L, Chang J, Cihan A, Fazio M, Chen CW, Zhu N, Koche R, Dzhekieva L, Ibáñez G, Dias S, Banka D, Krivtsov A, Luo M, Roeder RG, Bradner JE, Bernt KM, Armstrong SA. AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes. Cancer Cell. 2014 Dec 8;26(6):896-908. doi: 10.1016/j.ccell.2014.10.009. Epub 2014 Nov 20. PMID: 25464900; PMCID: PMC4291116. Sinha S, Barbosa K, Cheng K, Leiserson MDM, Jain P, Deshpande A, Wilson DM 3rd, Ryan BM, Luo J, Ronai ZA, Lee JS, Deshpande AJ, Ruppin E. A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing. Nat Commun. 2021 Nov 11;12(1):6512. doi: 10.1038/s41467-021-26788-6. Erratum in: Nat Commun. 2022 May 16;13(1):2828. doi: 10.1038/s41467-022-30475-5. PMID: 34764240; PMCID: PMC8586238.   Related Episodes Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard) The Menin-MLL Complex and Small Molecule Inhibitors (Yadira Soto-Feliciano) MLL Proteins in Mixed-Lineage Leukemia (Yali Dou)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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  • Beyond Mom: Rethinking Paternal Influence in Epigenetic Inheritance (Raffaele Teperino)
    In this episode Dr. Raffaele Teperino shares insights from his ongoing research focused on developmental programming, particularly how paternal health before conception influences not only offspring health but also maternal health outcomes. As we trace his academic journey from studying biotechnology and pharmacology to leading his own lab, Dr. Teperino reflects on his early fascination with medicine, the pivotal experiences that shaped his career, and the integration of epigenetics into understanding metabolic diseases. We discuss the nuances of epigenetics—going beyond simple chromatin biology to examine its wider implications on phenotypic variation. Dr. Teperino emphasizes his approach of modeling relevant physiological phenomena in the lab to better understand the underlying mechanisms driving conditions like obesity and metabolic disruption. A particular focus is placed on his experiences during his postdoctoral years, where he investigated the developmental pathways of hedgehog signaling and its metabolic implications in adipogenesis. Our talk shifts towards the practical implications of his research, highlighting recent investigations into how circadian rhythms and paternal lifestyles influence offspring health. Dr. Teperino reveals his findings on how disturbances in circadian rhythms can lead to intergenerational health issues, showcasing the surprising effects observed in offspring of fathers experiencing circadian misalignment. We delve into the significance of seminal fluid as a potential medium for intergenerational transfer of stress responses, examining the role of stress hormones and their impacts on fetal development. As we explore a fascinating recent study highlighting the impact of paternal diets on future generations, Dr. Teperino underscores the importance of understanding the shorter exposure periods sufficient to trigger these health changes. He presents data that links paternal obesity and preconception health to an increased risk of obesity and insulin resistance in children, challenging traditional narratives around maternal responsibility for offspring health.   References Darr J, Tomar A, Lassi M, Gerlini R, Berti L, Hering A, Scheid F, Hrabě de Angelis M, Witting M, Teperino R. iTAG-RNA Isolates Cell-Specific Transcriptional Responses to Environmental Stimuli and Identifies an RNA-Based Endocrine Axis. Cell Rep. 2020 Mar 3;30(9):3183-3194.e4. doi: 10.1016/j.celrep.2020.02.020. PMID: 32130917. Lassi M, Tomar A, Comas-Armangué G, Vogtmann R, Dijkstra DJ, Corujo D, Gerlini R, Darr J, Scheid F, Rozman J, Aguilar-Pimentel A, Koren O, Buschbeck M, Fuchs H, Marschall S, Gailus-Durner V, Hrabe de Angelis M, Plösch T, Gellhaus A, Teperino R. Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors. Sci Adv. 2021 May 26;7(22):eabg6424. doi: 10.1126/sciadv.abg6424. PMID: 34039610; PMCID: PMC8153725. Tomar A, Gomez-Velazquez M, Gerlini R, Comas-Armangué G, Makharadze L, Kolbe T, Boersma A, Dahlhoff M, Burgstaller JP, Lassi M, Darr J, Toppari J, Virtanen H, Kühnapfel A, Scholz M, Landgraf K, Kiess W, Vogel M, Gailus-Durner V, Fuchs H, Marschall S, Hrabě de Angelis M, Kotaja N, Körner A, Teperino R. Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs. Nature. 2024 Jun;630(8017):720-727. doi: 10.1038/s41586-024-07472-3. Epub 2024 Jun 5. PMID: 38839949; PMCID: PMC11186758.   Related Episodes The Impact of Paternal Diet on Offspring Metabolism (Upasna Sharma) Transgenerational Inheritance and Evolution of Epimutations (Peter Sarkies) The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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  • Evolutionary Epigenetic Clocks and Epigenetic Inheritance in Plants (Frank Johannes)
    In this episode of the Epigenetics Podcast, we talked with Dr. Frank Johannes from the Technical University of Munich in Freising about his work on evolutionary clocks and epigenetic inheritance in plants. In this episode we discuss Dr. Johannes pursuits in understanding how heritable epigenetic variations, particularly through DNA methylation, affect phenotypic diversity in plants. He shared insights about groundbreaking research initiatives he has led, including one of the first population epigenetic studies in plants that effectively linked heritable DNA methylation changes to critical traits like flowering time and root length. This work underscored the importance of epigenetic factors that extend beyond traditional genetic sequences, illustrating a significant shift in how we comprehend inheritance and trait variation in organisms. As we dug deeper into the science, we examined Dr. Johannes's innovative approaches to studying chromatin-based mechanisms of genome regulation, allowing for a nuanced understanding of epigenetic inheritance. His lab’s extensive phenotyping of Arabidopsis plants highlighted how inducing heritable variations in DNA methylation could lead to significant trait outcomes – results that have substantial implications for agriculture and understanding complex characteristics across generations. The dialogue continued to unravel the dynamics between forward and backward epimutations, delving into their heritable nature and their rapid accumulation compared to traditional genetic mutations. Dr. Johannes overturned conventional understanding by presenting epigenetic processes that are not as static as once thought, providing compelling evidence that these spontaneous changes could inform evolutionary clocks; a concept that offers new avenues for studying the relationships between species over relatively short timeframes. Moreover, we discussed the exciting concept of epigenetic clocks, which play a role in assessing the age of various species, including trees. The potential applications for such clocks in environmental management and the assessment of tree vitality further illuminated the practical impacts of Dr. Johannes's research. These insights also pave the way for sophisticated non-invasive methods of understanding plant biology, which can revolutionize forest management practices in the face of climate change and other ecological pressures.   References Colomé-Tatché M, Cortijo S, Wardenaar R, Morgado L, Lahouze B, Sarazin A, Etcheverry M, Martin A, Feng S, Duvernois-Berthet E, Labadie K, Wincker P, Jacobsen SE, Jansen RC, Colot V, Johannes F. Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16240-5. doi: 10.1073/pnas.1212955109. Epub 2012 Sep 17. PMID: 22988127; PMCID: PMC3479620. Cortijo S, Wardenaar R, Colomé-Tatché M, Gilly A, Etcheverry M, Labadie K, Caillieux E, Hospital F, Aury JM, Wincker P, Roudier F, Jansen RC, Colot V, Johannes F. Mapping the epigenetic basis of complex traits. Science. 2014 Mar 7;343(6175):1145-8. doi: 10.1126/science.1248127. Epub 2014 Feb 6. PMID: 24505129. van der Graaf A, Wardenaar R, Neumann DA, Taudt A, Shaw RG, Jansen RC, Schmitz RJ, Colomé-Tatché M, Johannes F. Rate, spectrum, and evolutionary dynamics of spontaneous epimutations. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6676-81. doi: 10.1073/pnas.1424254112. Epub 2015 May 11. PMID: 25964364; PMCID: PMC4450394. Yao N, Zhang Z, Yu L, Hazarika R, Yu C, Jang H, Smith LM, Ton J, Liu L, Stachowicz JJ, Reusch TBH, Schmitz RJ, Johannes F. An evolutionary epigenetic clock in plants. Science. 2023 Sep 29;381(6665):1440-1445. doi: 10.1126/science.adh9443. Epub 2023 Sep 28. PMID: 37769069.   Related Episodes Transgenerational Inheritance and Epigenetic Imprinting in Plants (Mary Gehring) Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: [email protected]
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