Podcasts about Molecular Cell

In this episode of the Epigenetics Podcast, we talked with Yali Dou from Keck School of Medicine of USC about her work on MLL Proteins in Mixed-Lineage Leukemia. To start off this Interview Yali describes her early work on MLL1 and its function in transcription, particularly its involvement in histone modification. She explains her successful purification of the MLL complex and the discovery of MOF as one of the proteins involved. Next, the interview focuses on her work in reconstituting the MLL core complex and the insights gained from this process. She shares her experience of reconstituting the MLL complex and discusses her focus on the crosstalk of H3K4 and H3K79 methylation, regulated by H2BK34 ubiquitination. The podcast then delves into the therapeutic potential of MLL1, leading to the discovery of a small molecule inhibitor. Finally, we talk about the importance of the protein WDR5 in the assembly of MLL complexes and how targeting the WDR5-ML interaction can inhibit MLL activity.   References Dou, Y., Milne, T., Ruthenburg, A. et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol 13, 713–719 (2006). https://doi.org/10.1038/nsmb1128 Wu, L., Zee, B. M., Wang, Y., Garcia, B. A., & Dou, Y. (2011). The RING Finger Protein MSL2 in the MOF Complex Is an E3 Ubiquitin Ligase for H2B K34 and Is Involved in Crosstalk with H3 K4 and K79 Methylation. Molecular Cell, 43(1), 132–144. https://doi.org/10.1016/j.molcel.2011.05.015 Cao, F., Townsend, E. C., Karatas, H., Xu, J., Li, L., Lee, S., Liu, L., Chen, Y., Ouillette, P., Zhu, J., Hess, J. L., Atadja, P., Lei, M., Qin, Z. S., Malek, S., Wang, S., & Dou, Y. (2014). Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia. Molecular Cell, 53(2), 247–261. https://doi.org/10.1016/j.molcel.2013.12.001 Park, S.H., Ayoub, A., Lee, YT. et al. Cryo-EM structure of the human MLL1 core complex bound to the nucleosome. Nat Commun 10, 5540 (2019). https://doi.org/10.1038/s41467-019-13550-2   Related Episodes Dosage Compensation in Drosophila (Asifa Akhtar) Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on X Active Motif on LinkedIn Email: podcast@activemotif.com

Die Themen in den Wissensnachrichten: +++ Kleine Gruppen sind kreativer als große +++ Weiterer möglicher Biomarker für Long Covid +++ Babyrobben-Boom auf Helgoland +++**********Weiterführende Quellen zu dieser Folge:It takes two to think/ Nature Biotechnology, 08.01.2024Persistent complement dysregulation with signs of thromboinflammation in active Long Covid/ Science, 19.01.2024Public preference for the rewilding framework: A choice experiment in the Oder Delta/ People and Nature, 21.01.2024Megalodon body form/ Palaeontologie Electronica, Januar 2024SATB2 organizes the 3D genome architecture of cognition in cortical neurons/ Molecular Cell, 19.01.2024Alle Quellen findet ihr hier.**********Ihr könnt uns auch auf diesen Kanälen folgen: Tiktok und Instagram.

In this episode of the Epigenetics Podcast, we talked with Kyle Eagen from Baylor College of Medicine about his work on BET Proteins and their role in chromosome folding and compartmentalization. In the early days of his research career Dr. Eagen made use of genomics and microscopy to study chromosomes, particularly polytene chromosomes in Drosophila. The correlation between the folding patterns detected by Hi-C and polytene bands highlights the similarities between the two, bridging traditional cytology with modern NGS methods. This work formed the basis of Kyle's thesis and sparked his interest in nuclear organization and chromosome 3D structure. In his independent lab Kyle then studied compartments in chromatin structure and focused on the relationship between histone modifications and the 3D structure of chromosomes. The discovery of BRD4-NUT, a fusion oncoprotein that reprograms chromosome 3D structure, is highlighted as a significant step forward in understanding chromatin structure. The conversation then shifts to the use of a tool to test hypotheses about the involvement of BRD4 in a specific process, leading to consistent results and considerations for manipulating chromosome organization for therapeutic purposes. The role of BET proteins in genome folding and the need for further research on other factors involved in 3D genome structure are discussed.   References Rosencrance, C. D., Ammouri, H. N., Yu, Q., Ge, T., Rendleman, E. J., Marshall, S. A., & Eagen, K. P. (2020). Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment. Molecular Cell, 78(1), 112-126.e12. https://doi.org/10.1016/j.molcel.2020.03.018 Huang, Y., Durall, R. T., Luong, N. M., Hertzler, H. J., Huang, J., Gokhale, P. C., Leeper, B. A., Persky, N. S., Root, D. E., Anekal, P. V., Montero Llopis, P. D. L. M., David, C. N., Kutok, J. L., Raimondi, A., Saluja, K., Luo, J., Zahnow, C. A., Adane, B., Stegmaier, K., … French, C. A. (2023). EZH2 Cooperates with BRD4-NUT to Drive NUT Carcinoma Growth by Silencing Key Tumor Suppressor Genes. Cancer Research, 83(23), 3956–3973. https://doi.org/10.1158/0008-5472.CAN-23-1475   Related Episodes Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden) Genome Organization Mediated by RNA Polymerase II (Argyrys Papantonis) Analysis of 3D Chromatin Structure Using Super-Resolution Imaging (Alistair Boettiger)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on X Active Motif on LinkedIn Email: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Claudia Keller Valsecchi from the Institute for Molecular Biology in Mainz to talk about her work on gene dosage alterations in evolution and ageing. Claudia Keller-Valsecchi's team focuses on understanding the fundamental mechanisms of how cellular function in eukaryotes is influenced by gene copy number variation. Recent findings indicate that precise MSL2-mediated gene dosage is highly relevant for organismal development. Since 2020 Claudia Keller-Valsecchi runs her own lab at the IMB in Mainz, Germany, where she tries to understand from a molecular mechanistic point of view how gene dosage compensation works, with projects in mosquitoes and in Artemia franciscanagene, as well as dosage regulation in the mammalian system regarding development and disease.   References Keller, C., Adaixo, R., Stunnenberg, R., Woolcock, K. J., Hiller, S., & Bühler, M. (2012). HP1Swi6 Mediates the Recognition and Destruction of Heterochromatic RNA Transcripts. Molecular Cell, 47(2), 215–227. https://doi.org/10.1016/j.molcel.2012.05.009 Valsecchi, C.I.K., Basilicata, M.F., Georgiev, P. et al. RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature 589, 137–142 (2021). https://doi.org/10.1038/s41586-020-2935-z Keller Valsecchi, C. I., Marois, E., Basilicata, M. F., Georgiev, P., & Akhtar, A. (2021). Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila. Life Science Alliance, 4(9), e202000996. https://doi.org/10.26508/lsa.202000996   Related Episodes Epigenetics and X-Inactivation (Edith Heard) Dosage Compensation in Drosophila (Asifa Akhtar)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

Special guest Carrie Vyhlidal, PhD of KCAS joins John and Dom in the 68th episode of "The Weekly Bioanalysis" to discuss the ways molecular cell & gene therapy services has evolved and why their role will likely become more and more important to the world of bioanalytical drug development in the future. They discuss everything from the history of Cell & Gene Therapies and the topic of replicates, to some of the challenges and pitfalls of GLP research for molecular cell & gene therapy specialists."The Weekly Bioanalysis" is a podcast dedicated to discussing Bioanalytical news, tools and services related to the Pharmaceutical, Biopharmaceutical and Biomarker industries. Every month, KCAS will bring you another 60 minutes (or so) of friendly banter between our two finest Senior Scientific Advisors as they chat over coffee and discuss what they've learned about the Bioanalytical world the past couple of weeks. The Weekly Bioanalysis is brought to you by KCAS.KCAS is a progressive growing contract research organization of well over 250 talented and dedicated individuals with growing operations in Kansas City, Doylestown, PA, and Lyon, France, where we are committed to serving our clients and improving health worldwide. Our experienced scientists provide stand-alone bioanalytical services to the Pharmaceutical, Biopharmaceutical, Animal Health and Medical Device industries.

In this episode of the Epigenetics Podcast, we caught up with Jop Kind from Hubrecht Institute to talk about his work on single cell DamID, EpiDamID, and Lamina Associated Domains (LADs). Jop Kind started out developing single cell DamID (scDamID), based on the DamID technique. First, this technique was adapted to a microscopic readout which enabled them to follow the localisation of chromatin domains after cell division. Next, the lab expanded this technique into the NGS space and created genome-wide maps of nuclear lamina Interactions in single human cells. Since LADs are in a heterochromatic chromatin context, the lab expanded scDamID into the epigenetic space. They first combined it with a transcriptional readout.  Later-on they developed EpiDamID, a method to target a diverse set of chromatin types by taking advantage of the binding specificities of single-chain variable fragment antibodies, engineered chromatin reader domains, and endogenous chromatin-binding proteins.   References Kind, J., Pagie, L., Ortabozkoyun, H., Boyle, S., de Vries, S. S., Janssen, H., Amendola, M., Nolen, L. D., Bickmore, W. A., & van Steensel, B. (2013). Single-Cell Dynamics of Genome-Nuclear Lamina Interactions. Cell, 153(1), 178–192. https://doi.org/10.1016/j.cell.2013.02.028 Kind, J., Pagie, L., de Vries, S. S., Nahidiazar, L., Dey, S. S., Bienko, M., Zhan, Y., Lajoie, B., de Graaf, C. A., Amendola, M., Fudenberg, G., Imakaev, M., Mirny, L. A., Jalink, K., Dekker, J., van Oudenaarden, A., & van Steensel, B. (2015). Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells. Cell, 163(1), 134–147. https://doi.org/10.1016/j.cell.2015.08.040 Borsos, M., Perricone, S.M., Schauer, T. et al. Genome–lamina interactions are established de novo in the early mouse embryo. Nature 569, 729–733 (2019). https://doi.org/10.1038/s41586-019-1233-0 Markodimitraki, C. M., Rang, F. J., Rooijers, K., de Vries, S. S., Chialastri, A., de Luca, K. L., Lochs, S. J. A., Mooijman, D., Dey, S. S., & Kind, J. (2020). Simultaneous quantification of protein–DNA interactions and transcriptomes in single cells with scDam&T-seq. Nature Protocols, 15(6), 1922–1953. https://doi.org/10.1038/s41596-020-0314-8 Rang, F. J., de Luca, K. L., de Vries, S. S., Valdes-Quezada, C., Boele, E., Nguyen, P. D., Guerreiro, I., Sato, Y., Kimura, H., Bakkers, J., & Kind, J. (2022). Single-cell profiling of transcriptome and histone modifications with EpiDamID. Molecular Cell, 82(10), 1956-1970.e14. https://doi.org/10.1016/j.molcel.2022.03.009   Related Episodes Dosage Compensation in Drosophila (Asifa Akhtar) Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff) Single Cell Epigenomics in Neuronal Development (Tim Petros)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

We are honored to have Dr. Jennifer Morgan joining us for today's episode! Dr. Morgan is a Senior Scientist and Director of the Eugene Bell Center for Regenerative Biology and Tissue Engineering at the Marine Biological Laboratory (MBL) in Woods Hole, MA.She received her Ph.D. in Neurobiology from Duke University, where she worked on mechanisms of neurotransmission. She then carried out her postdoctoral studies on membrane trafficking in the Cell Biology Department at Yale University. In 2007, Morgan joined the Section of Molecular Cell and Developmental Biology at The University of Texas at Austin as an Assistant Professor where she expanded her research program to include spinal cord injury and regeneration mechanisms. Dr. Morgan received her first research grant from the Morton Cure Paralysis Fund, which eventually led to a Research Project Grant (R01) from the National Institutes of Health that is now in its 11th year of funding. While at UT-Austin, Dr. Morgan received several prestigious awards, including a University of Texas Regents' Outstanding Teaching Award (2011) and the Janett Trubatch Career Development Award from the Society for Neuroscience (2011). In 2012, Dr. Morgan was recruited to the MBL's Bell Center to expand her research program in regenerative biology. She continues to study the mechanisms of neurotransmission under both normal conditions, as well as with spinal injury and neurodegenerative disorders such as Parkinson's disease. Dr. Morgan is currently one of the co-directors of the NIH-funded courses at the MBL called “Frontiers in Stem Cells and Regeneration”, and she is a standing member on the NIH Neuronal Communications Study Section. Throughout her career, Dr. Morgan has dedicated her efforts to mentoring students and postdocs and advancing diversity and inclusion in the STEM sciences, and she is actively involved in the MBL Diversity and Inclusion Advisory Committee, which she chaired for the last 3 years.Marine Biological Laboratory: https://www.mbl.edu/ Many thanks to Dr. Morgan for her work and for being our guest on today's episode! This production is a collaborative effort of volunteers working to create a quality audio and visual experience around the subject of spinal cord injury. A special shout out of appreciation to Clientek for providing studio space and top-notch recording equipment. Most importantly, thank YOU for being part of the Spinal Cast audience!Interested in watching these episodes?! Check out our YouTube playlist! https://youtube.com/playlist?list=PL40rLlxGS4VzgAjW8P6Pz1mVWiN0Jou3v If you'd like to learn more about the MCPF you can visit our website - https://mcpf.org/ Donations are always welcomed - https://mcpf.org/you-can-help/

Lovisa Afzelius is an origination partner at Flagship Pioneering and the former SVP of Strategy & Operations at Flagship-founded Cogen Immune Medicines, now known as Repertoire Immune Medicines. A computational scientist by training, she has two decades of leadership experience and a passion for data-driven drug discovery, from early inception to clinical development across multiple therapeutic areas. Previously, Lovisa built and led Pfizer's systems immunology function and served as executive director of clinical programs. In this role, she launched several Phase II studies across autoimmune indications and as a member of the Inflammation & Immunology Research Unit leadership team, Lovisa co-managed the portfolio from early target discovery to Phase II clinical trials across all immunological assets. In addition, she served on Pfizer's Worldwide R&D Data Strategy Committee. In 2017, Lovisa co-founded Elsa.science, a digital health company in the rheumatoid arthritis space where she serves as chairman of the board. She also serves on the board of the Swedish New England Chamber of Commerce. Before moving to the US in 2013, Lovisa was CEO of BioChromix Pharma. Lovisa began her career at AstraZeneca as Project Director, Global In Vitro Metabolism Leader and Computational Chemist across cardiovascular, metabolic, and neurodegenerative diseases. Lovisa has received numerous accolades for her work: she was included in the top 100 ​“most influential persons under age 40 in Sweden” by Affärsvärlden, and ​“scientist of tomorrow” at the European Federation of Pharmaceutical Industries and Associations' 30th anniversary. Lovisa received the Rosenön Award for best thesis of the year within the field of pharmacodynamics/​pharmacokinetics in Sweden. Lovisa holds a Ph.D. in computational chemistry from Uppsala University, a Master of Science in integrative pharmacology from Gothenburg University as well as an M.B.A. from the MIT Sloan School of Management. Theonie is a principal at Flagship Pioneering where she conceives, builds and grows the science, intellectual property and business strategy that form the foundation of Flagship's next breakthrough startups. She co-founded Alltrna and serves as its chief innovation officer. Prior to joining Flagship, Theonie completed her graduate studies in cell and molecular biology at the Perelman School of Medicine at the University of Pennsylvania. Her research focused on replication fork dynamics in the context of cancer development and therapeutics. Theonie has received several awards and has been granted multiple fellowships for her academic work, including an NIH NRSA Predoctoral Fellowship. During her graduate studies, Theonie held multiple leadership positions on Executive and Curriculum Committees. She also completed a Wharton Business Foundations Specialization and was a mentor at the yearly Larta Institute NIH CAP FeedForward Sessions. Theonie is a Business Advisory Board member of the Harvard Institute for RNA Medicine and a member of the Bioscience & Investor Inclusion Group (BIIG) Diverse Talent Network Group. Theonie's work has resulted in multiple pending patents and publications, including articles in Nature Biotechnology, Molecular Cell and Journal of Biological Chemistry.

In this episode of the Epigenetics Podcast, we caught up with Emily Bernstein from Icahn Schoon of Medicine at Mount Sinai to talk about her work on MacroH2A function and the role of Polycomb proteins in its epigenetic regulation, and how this affects in stem cell development and disease. The Bernstein Lab focuses on histone variants, in particular the variants of macroH2A. Chromatin architecture is influenced by the composition of the nucleosome and, hence, exchanging the core histones for histone variants can have a major impact on chromatin structure. MacroH2A is the histone with the most variants, due to a 30kDa non-histone domain (macro domain) at their C-termini. This variation leads to many macroH2A variants, which have been found to have regulatory roles in the cell. Among other things the Bernstein Lab has shown that macroH2A is enriched at a critical set of Utx target genes whose expression is critical for the early stages of induced pluripotency.   References Kapoor, A., Goldberg, M. S., Cumberland, L. K., Ratnakumar, K., Segura, M. F., Emanuel, P. O., Menendez, S., Vardabasso, C., LeRoy, G., Vidal, C. I., Polsky, D., Osman, I., Garcia, B. A., Hernando, E., & Bernstein, E. (2010). The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature, 468(7327), 1105–1109. https://doi.org/10.1038/nature09590 Vardabasso, C., Gaspar-Maia, A., Hasson, D., Pünzeler, S., Valle-Garcia, D., Straub, T., Keilhauer, E. C., Strub, T., Dong, J., Panda, T., Chung, C.-Y., Yao, J. L., Singh, R., Segura, M. F., Fontanals-Cirera, B., Verma, A., Mann, M., Hernando, E., Hake, S. B., & Bernstein, E. (2015). Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma. Molecular Cell, 59(1), 75–88. https://doi.org/10.1016/j.molcel.2015.05.009 Sun, Zhen, Dan Filipescu, Joshua Andrade, Alexandre Gaspar-Maia, Beatrix Ueberheide, and Emily Bernstein. 2018. “Transcription-Associated Histone Pruning Demarcates MacroH2A Chromatin Domains.” Nature Structural & Molecular Biology 25(10):958–70. doi: 10.1038/s41594-018-0134-5.   Related Episodes Influence of Histone Variants on Chromatin Structure and Metabolism (Marcus Buschbeck) Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni) Variants of Core Histones: Modulators of Chromatin Structure and Function (Sandra Hake)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Efrat Shema from the Weizmann Institute of Science to talk about her work on Single Molecule Imaging of chromatin, and the analysis of nucleosomes circulating in plasma. In ChIP-Seq experiments the peak you get as a read out represents an average over, most often, millions of cells. Furthermore, one often does not know if that peak represents one or more than one nucleosome. If you then want to study multiple marks at the same time, the question remains: do those modifications occur at the same time, in the same cell? The Laboratory of Efrat Shema works on answering those questions by developing methods to study the modification patterns on single nucleosomes with single molecule imaging. With that it is possible to study single nucleosomes in a high throughout manner to identify the modifications they are decorated with. A subsequent sequencing step makes it possible to identify the genomic location of that nucleosome.   References Shema, E., Bernstein, B. E., & Buenrostro, J. D. (2019). Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution. Nature Genetics, 51(1), 19–25. https://doi.org/10.1038/s41588-018-0290-x Shema, E., Jones, D., Shoresh, N., Donohue, L., Ram, O., & Bernstein, B. E. (2016). Single-molecule decoding of combinatorially modified nucleosomes. Science, 352(6286), 717–721. https://doi.org/10.1126/science.aad7701 Shema, E., Kim, J., Roeder, R. G., & Oren, M. (2011). RNF20 Inhibits TFIIS-Facilitated Transcriptional Elongation to Suppress Pro-oncogenic Gene Expression. Molecular Cell, 42(4), 477–488. https://doi.org/10.1016/j.molcel.2011.03.011 Shema, E., Tirosh, I., Aylon, Y., Huang, J., Ye, C., Moskovits, N., Raver-Shapira, N., Minsky, N., Pirngruber, J., Tarcic, G., Hublarova, P., Moyal, L., Gana-Weisz, M., Shiloh, Y., Yarden, Y., Johnsen, S. A., Vojtesek, B., Berger, S. L., & Oren, M. (2008). The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes & Development, 22(19), 2664–2676. https://doi.org/10.1101/gad.1703008   Related Episodes ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro) Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot) The Past, Present, and Future of Epigenetics (Joe Fernandez, founder of Active Motif)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Serena Sanulli from Stanford University to talk about her work on Heterochromatin Protein 1 (HP1), the structure of chromatin on the atomic-scale and the meso-scale, and phase separation. The Laboratory of Serena Sanulli is interested in finding connections between changes that happen on the nucleosomal level and the resulting impact on chromatin conformation on the meso-scale. They combine methods like NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology and Genetics. This enables them to dissect how cells use the diverse biophysical properties of chromatin to regulate gene expression across length and time scales. A second focus of the lab is HP1, which interacts with the nucleosome and changes its conformation, enabling the compaction of the genome into heterochromatin, effectively silencing genes in that region. A high concentration of HP1 leads to the phenomenon of phase separation in the nucleus, which the Sanulli lab is now investigating.   References Sanulli, S., Justin, N., Teissandier, A., Ancelin, K., Portoso, M., Caron, M., Michaud, A., Lombard, B., da Rocha, S. T., Offer, J., Loew, D., Servant, N., Wassef, M., Burlina, F., Gamblin, S. J., Heard, E., & Margueron, R. (2015). Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation. Molecular Cell, 57(5), 769–783. https://doi.org/10.1016/j.molcel.2014.12.020 Sanulli, S., Trnka, M. J., Dharmarajan, V., Tibble, R. W., Pascal, B. D., Burlingame, A. L., Griffin, P. R., Gross, J. D., & Narlikar, G. J. (2019). HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature, 575(7782), 390–394. https://doi.org/10.1038/s41586-019-1669-2 Sanulli, S., & Narlikar, G. J. (2021). Generation and Biochemical Characterization of Phase‐Separated Droplets Formed by Nucleic Acid Binding Proteins: Using HP1 as a Model System. Current Protocols, 1(5). https://doi.org/10.1002/cpz1.109   Related Episodes Transcription and Polycomb in Inheritance and Disease (Danny Reinberg) Heterochromatin and Phase Separation (Gary Karpen)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

As we approach the end of 2020, according to the U.S. National Cancer Institute (NCI), we have had approximately 1,806,590 new cases of cancer diagnosed in the United States, with 606,520 deaths. Cancer continues to be the leading causes of death worldwide. In 2018, there were 18.1 million new cases and 9.5 million cancer-related deaths worldwide. By 2040, the number of new cancer cases per year is expected to rise to 29.5 million and the number of cancer-related deaths to 16.4 million. Dr. Azra Raza, MD, is the Chan Soon-Shiong Professor of Medicine, in the Department of Medicine, Division of Hematology / Oncology, and Director of the Myelodysplastic Syndrome (MDS) Center, at the Columbia University Medical Center. Previously, Dr. Raza was the Chief of Hematology-Oncology and the Gladys Smith Martin Professor of Oncology at the University of Massachusetts. Dr. Raza is an international authority on pre-leukemia / MDS, and acute leukemia, and is both a physician and scientist who divides her time equally between caring for patients and supervising a state-of-the-art basic research lab which is well-funded by multiple large grants. Dr. Raza started collecting blood and marrow samples on her patients in 1984 and now her Tissue Bank, the largest and oldest in the country with over 60,000 samples, is considered a unique national treasure. Dr. Raza has published her original clinical and basic research comprising over 300 peer-reviewed manuscripts in high profile journals like Nature, New England Journal of Medicine, Cell, Molecular Cell, Cancer Research, Blood, Leukemia. She has published over 1,000 abstracts, dozens of book chapters and edited a book devoted to MDS, entitled "Myelodysplastic Syndromes & Secondary Acute Myelogenous Leukemia: Directions for the New Millennium". Dr. Raza is the recipient of numerous awards including The Hope Award in Cancer Research 2012 (shared with the Nobel Laureate Dr. Elizabeth Blackburn). She was named as one of the 100 Women Who Matter by Newsweek Pakistan. Dr. Raza is a member of the Founder Group designing Breakthrough Developments in Science and Technology with President Bill Clinton, and was involved with Vice President Joe Biden to discuss the Cancer Moonshot initiative. Dr. Raza is the author of the recently published book "The First Cell: And the Human Costs of Pursuing Cancer to the Last". In addition to her scientific accomplishments, Dr. Raza is a dedicated reader of Urdu literature, and co-authored a book on the poems of the 19th century Indian poet Ghalib, entitled "Ghalib: Epistemologies of Elegance". 

Thursday, February 18, 2021 at 07:00 PM (PST) Speakers: Dr. Azra Raza (Cancer Specialist and Researcher) Dr. Samia Altaf (Public Health Specialist)   Moderator: Dr. Nadeem ul Haque (VC PIDE)   Dr. Azra Raza is the Chan Soon-Shiong Professor of Medicine and Director of the MDS Center at Columbia University in New York. Previously, she was the Chief of Hematology-Oncology and the Gladys Smith Martin Professor of Oncology at the University of Massachusetts. She is considered an international authority on pre-leukemia (MDS) and acute leukemia. Dr. Raza has published her original clinical and basic research comprising over 300 peer-reviewed manuscripts in high profile journals like Nature, New England Journal of Medicine, Cell, Molecular Cell, Cancer Research, Blood, Leukemia. She has published >1000 abstracts, dozens of book chapters and edited a book devoted to MDS. She is a sought after speaker in scientific circles and the recipient of numerous awards including The Hope Award in Cancer Research 2012 (shared with the Nobel Laureate Dr. Elizabeth Blackburn). She was named as one of the 100 Women Who Matter by Newsweek Pakistan. Dr. Raza is a member of the Founder Group designing Breakthrough Developments in Science and Technology with President Bill Clinton and met with Vice President Joe Biden to discuss the Cancer Moonshot initiative at his residence at the Naval Observatory in 2015. She is the author of The First Cell: And the human costs of pursuing cancer’s last published by Basic Books, October 2019. In addition to her scientific accomplishments, Dr. Raza is a dedicated reader of Urdu literature, the co-author of GHALIB: Epistemologies of Elegance.

Dr. Azra Raza is the Chan Soon-Shiong Professor of Medicine and Director of the MDS Center at Columbia University in New York. Previously, she was the Chief of Hematology-Oncology and the Gladys Smith Martin Professor of Oncology at the University of Massachusetts. She is considered an international authority on pre-leukemia (MDS) and acute leukemia and is one of those rare physician-scientists who divide their time equally between caring for patients and supervising a state-of-the-art basic research lab that is well-funded by multiple large grants. Dr. Raza started collecting blood and marrow samples on her patients in 1984 and now her Tissue Bank, the largest and oldest in the country with >60,000 samples, is considered a unique national treasure.Dr. Raza has published her original clinical and basic research comprising over 300 peer-reviewed manuscripts in high profile journals like Nature, New England Journal of Medicine, Cell, Molecular Cell, Cancer Research, Blood, Leukemia. She has published >1000 abstracts, dozens of book chapters and edited a book devoted to MDS. She is a co-editor of a website 3quarksdaily started by her brother Syed Abbas Raza.Dr. Raza and I discuss correcting cancer at its earliest footprints, why early detection is the key to survival, and the future of cancer technology. She is a sought-after speaker in scientific circles and the recipient of numerous awards including The Hope Award in Cancer Research 2012 (shared with the Nobel Laureate Dr. Elizabeth Blackburn). She was named as one of the 100 Women Who Matter by Newsweek Pakistan. Dr. Raza is a member of the Founder Group designing Breakthrough Developments in Science and Technology with President Bill Clinton and met with Vice President Joe Biden to discuss the Cancer Moonshot initiative at his residence at the Naval Observatory in 2015.Originally recorded on September 18, 2020Host, Earlina Green Hamilton

dessanをゲストに迎え、CRISPRの仕組みを利用した様々な技術や遺伝子回路、これからの発展について話しました。Show notes The Nobel Prize in Chemistry 2020…The Nobel Prize in Chemistry 2020 was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing.” Scientifc Background on the Nobel Prize in Chemistry 2020 A TOOL FOR GENOME EDITING…ノーベル財団による詳細なCRISPR研究のレビュー、そしてなぜDoudnaとCharpentierの二人が受賞に値するのかについて説明している。 76. The Chimeric RNA, Researchat.fm…ゲノム編集についてdessanをゲストに迎えて話しました。 A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science 2012…CharpentierとDoudnaによるノーベル賞につながる論文の一つ。CRISPR–Cas9システムがこの論文によってその大枠が明らかにされた。 Multiplex Genome Engineering Using CRISPR/Cas Systems. Science 2013…Feng Zhang labによるヒト細胞におけるゲノム編集技術の報告。 RNA-Guided Human Genome Engineering via Cas9. Science 2012…George Church labによるヒト細胞におけるゲノム編集技術の報告も同時に掲載された。 First rounders: Feng Zhang (Podcast)…Feng Zhangが出演したNatute Biotechnologyのポッドキャスト。おすすめです。 26. Cool tech googlability, Researchat.fm…RNAを標的にできるCas13bについては、エピソード26で紹介しました。 Cas14 (crisp_bio)…“Cas14は、PAMに依存しないssDNA切断活性に加えて、PAMに依存するdsDNA切断活性も帯びている” CasX enzymes comprise a distinct family of RNA-guided genome editors. Nature 2019…CasX Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration. Nature 2019…トランスポゾン型のCasシステムの報告。 RNA-programmed genome editing in human cells. eLife 2013…Doudna labによるヒト細胞におけるゲノム編集技術の報告。FengやChurchらよりも少しだけ遅かった。 Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9. Nature Communications 2014 Ep52. Split into a row Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity. Cell 2013…Double nicking (2つのgRNAとCas9 nickase)によるより正確なゲノム編集方法が示された。 Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 2015…Cas9を用いた転写の活性化手法。 Live visualization of chromatin dynamics with fluorescent TALEs. Nature Structural & Molecular Biology 2013 … TALENを用いた染色体の特定領域のイメージング方法 Dynamic Imaging of Genomic Loci in Living Human Cells by an Optimized CRISPR/Cas System. Cell 2013…dCas9-EGFPによる生細胞のイメージング技術。SpCas9の場合は、D10AとH840Aの２つの変異を入れることで、DNAに結合するが切断しないdead Cas9 (dCas9)として利用することができる。 Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nature Communications 2017…ガイドRNAにMS2 loopをたくさんつなげることで (14個!)、明るい輝点を得ることができる。 CRISPR-mediated live imaging of genome editing and transcription. Science 2019…こちらは蛍光標識したガイドRNAを利用した生細胞イメージング方法。 A protein tagging system for signal amplification in gene expression and fluorescence imaging. Cell 2014…Sun tagとCas9を用いたイメージング方法。 Split Green Fluorescent Proteins: Scope, Limitations, and Outlook…Split GFP Programmable RNA tracking in Live Cells with CRISPR/Cas9. Cell 2016…PAMmerによるSpCas9のmRNAイメージング CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization. Cell 2018 … CRISPR-GO：CRISPR技術、核内でのゲノム空間構造、ポッドキャスト内ではゲノム同士を寄せるという説明をしていましたが、今調べてみると特定のゲノム領域と核膜やカハール体への再配置ということでした。 Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nature Communications 2017 … こちらがCRISPRの仕組みを用いることで人工的に染色体内部にループを作成した論文。 Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 2008 … LacO-LacIの仕組みを用いることでゲノムの特定領域にLacO arrayを差し込み、核膜に局在させたLacIに結合させることである遺伝子領域を核膜側に誘導しようとした論文。最初にこの論文を読んだ時はそのアイデアにたまげました。 9. One-shot beautiful experiment (Researchat.fm)…人工的なDNA領域へ細胞内の情報（細胞系譜）を書き込む技術についてエピソード9で話しました。 CRISPR–Cas encoding of a digital movie into the genomes of a population of living bacteria. Nature 2017…George Churchらは、Cas1-Cas2システムによって馬の動画をバクテリアゲノム書き込み、それを読み出すことに成功した。 Multiplex recording of cellular events over time on CRISPR biological tape. Science 2017…コピー数の異なる2つのプラスミドをCas1-Cas2で取り込ませて、細胞内で人工的な時計のような仕組みを実現した。 Single-Nucleotide-Resolution Computing and Memory in Living Cells. Molecular Cell 2019…Tim Liu Labによる複雑な遺伝子回路の実現。DOMINOについては、プロモーター配列を標的にしているのではなくオペレーター配列でした。 Rewritable multi-event analog recording in bacterial and mammalian cells. Science 2018…David Liu labから報告されたガイドRNAによって連鎖する遺伝子回路（カスケード）の実現。 Terminal Deoxynucleotidyl Transferase, TdT…テンプレートに依存しないDNA合成を可能にする酵素。 Tandem fluorescent protein timers for in vivo analysis of protein dynamics. Nature Biotechnology 2012…GFP Timer Permanent genetic memory with >1-byte capacity. Nature Methods 2014 Continuous genetic recording with self-targeting CRISPR-Cas in human cells. Science 2016…自分で自分のガイドRNAを編集することで、理論的には無限に情報を書き込む方法が提案されたが、領域が壊れてしまう問題もある。 Ten Simple Rules to Win a Nobel Prize. ヘンリー・ブラッグ (Wikipedia) iPS細胞 (Wikipedia) 国境なき医師団 Human Genome Project Xiaowei Zhuang Expansion microscopy (Wikipedia) Renato Dulbecco (Wikipedia) Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nature Biotechnology 2019…LEAPER crisp_bio … 世界広しといえでも、これだけCRISPRの最新情報がまとまっているサイトはCRISP_BIOさんの他に世の中には存在しません。日本語でCRISPRの最先端情報を追える喜び。CRISP_BIOさん、いつもありがとうございます。 Editorial notes 1分でわかるとか無理なのですが、一方で言葉を尽くせばわかる可能性についても同時に信じておりますので…(soh) 思い出しながらどんどん話しているので、後から聞き返すと細部が間違っていたりしています。気になった方はshow notesをご参照ください。(dessan) いい感じのグルーヴがみられてよかったです。ポッドキャストやってきてよかったです。(tadasu) 最初に喋らんと出番が無くなる！と思ってこれまでの流れをまとめてみたんですが細かく色々ミスってました…(coela)

ENCODEプロジェクトにおけるサイレンサー探索の論文紹介と現代生物学の複雑性と多様性について話しました。Shownotes ENCODE…ENCODEとはEncyclopedia of DNA Elementsの略！ ENCODE (Wikipedia) ヒトゲノムの機能解明に向けたENCODEの試み (pdf) Initial sequencing and analysis of the human genome. Nature 2001…ヒトゲノム解読の論文。 The Sequence of the Human Genome. Science 2001…ヒトゲノム解読の論文。 ENCODE 4…ENCODEのPhase 4についてはここにaimなどが書いてある。 ENCODE3勉強会…Sohも論文読みをしました。 ENCODE 3 paper collection…ENCODE 3の論文リストはここにあります。 DNase I hypersensitive site (Wikipedia) Systematic identification of silencers in human cells. Nature Genetics, 2020…今回Sohが解説する論文はこれです。　 転写制御因子 (脳科学辞典) … プロモーターやエンハンサー、サイレンサーまわりについて。遺伝子発現とは、遺伝子というDNA上にコードされた情報がいかにRNA、タンパク質として実体を伴って機能するかということであるのだが、この量を調節する機能、とくにDNA->RNAの段階(転写)で調節することを転写制御という。ここで重要となるのがプロモーターやエンハンサー、サイレンサー、さらにはインスレーターなどである。 遺伝子発現制御機構: クロマチン, 転写制御, エピジェネティクス (Amazon) … tadasuはこの本で一度転写周りを勉強しなおしたが、自分が思っていたプロモーターやエンハンサーと実際の定義はかなりズレがあったことを思い知らされた。 STARR-seq (Wikipedia)…ゲノム中に含まれるエンハンサーやプロモーター配列をバーコードと次世代シーケンサーを用いて大量にアッセイする方法の一つ。オリジナルの論文はここ: Genome-Wide Quantitative Enhancer Activity Maps Identified by STARR-seq, Science 2013 Caspase-9 (Wikipedia)…Caspase9はアポトーシスを担う重要なタンパク質の一つ。 EF1aプロモーター…ヒトやマウスの細胞の中で高い活性を持つ恒常発現プロモーターのうちの一つ。CMVプロモーターも使われることが多い。 サイレンサー…哺乳動物細胞における転写を制御する配列のうち、転写活性に対して抑制的に働く配列を指しています。恒常発現プロモーターの下流にあるとそのさらに下流にある遺伝子発現を強く抑制する配列（200bp程度）を指しています。 ハウスキーピング遺伝子…細胞機能を維持するために常に発現している遺伝子。これを「恒常的な遺伝子発現」と呼んだりします。 K562…ヒト慢性骨髄性白血病由来の培養細胞株。 293T…ヒト胎児腎由来の培養細胞株。 HepG2…ヒト肝癌由来の細胞株。 ルシフェラーゼアッセイ pGL4.51[luc2/CMV/Neo] Vector…スクリーニングで見つかったサイレンサーはこのベクターを用いてルシフェラーゼアッセイによってその活性が調べられた。 ヒストン修飾 (Abcam) ヒストン (Wikipedia) Purification of Proteins Associated with Specific Genomic Loci. Cell, 2009.…PICh法を用いるとゲノムに結合したタンパク質を同定することができる。 Hi-C…Hi-Cについてはエピソード9などで話しました。 ChiA-PET (Wikipedia) FANTOM…“FANTOMは、理化学研究所のマウスゲノム百科事典プロジェクトで収集された完全長cDNAのアノテーション（機能注釈）を行うことを目的に、林崎良英博士が中心となり2000年に結成された国際研究コンソーシアムです” NIH Roadmap Epigenomics Mapping Consortium…ヒトのエピジェネティクスに関連する大量のデータを計測しアトラスを作ることを目的とした国際コンソーシアム。 Illumina Body Map 2.0 Human Cell Atras…ヒトの体を構成する全ての細胞の分類とマッピングを目指す国際共同プロジェクト。 4D Nucleome Project…染色体構造のマッピングのためのコンソーシアム。 The 4D nucleome project. Nature, Dekker at al 2017 The Cancer Genome Atlas Program (TCGA)…がんゲノムの大量のデータを収集している国際プロジェクト。 ゲノム編集とはなにか (ブルーバックス) (Amazon)…山本先生が書かれたゲノム編集について非常にわかりやすい本が出ております。ぜひ。 ep47, Researchat.fm…エピソード47ではCas13を用いた微量の核酸検出SHERLOCKやDETECTRについて紹介しています。 Advances in Chromatin and Chromosome Research: Perspectives from Multiple Fields. Molecular Cell, 2020 … tadasuが参加しているBoston Chromatin Clubで書いた筆頭著者17人のレビュー。 ep37, Biological Enigma, Researchat.fm…セントラルドグマを含む分子生物学の基礎についても話しました。 ep7, In the golden age of molecular biology … 遺伝暗号解明周りの研究について話しました。 ep9, One-shot beautiful experiment … 細胞系譜について ep2, An emerging technology is always not perfect … CRISPRとゲノム編集周辺について話しました。 Gene drive (Wikipedia) … 遺伝子ドライブ ワトソンの遺伝子の分子生物学 (Amazon) 後成説 (Wikipedia) … エピジェネシス。アリストテレスから始まる発生の理論。 前成説 (Wikipedia) 分子進化のほぼ中立説 偶然と淘汰の進化モデル (ブルーバックス) (Amazon) ep36, DNA-of-things … DNAを練りこんだ3Dプリンティング技術について話しました。 情報量 … 情報量、エントロピー シャノンの情報理論入門 (ブルーバックス) (Amazon) ファインマンの計算機科学 (Amazon) … tadasuおすすめの情報理論の教科書。ゲノムやセントラルドグマの話についての情報理論についても記述がある(あった気がする)。 Developmental Biology (Amazon) … 発生のGilbert本 Principles of Development (Amazon) … 発生のWolpert本 Molecular Biology of the Cell (NCBI) Shownotes 正直、プロモーターとかエンハンサーとかサイレンサーって言っていますが、実際にプロモーターとエンハンサーの違いなどよく考えるとわからなくなってきます。とても難しい。雰囲気でやっています。(soh) データは山のようにある。あとは君たち次第だ！(いいのかそれで？)(tadasu) 作業が楽しくても3日以上寝ないと空から奴らが襲ってくるので要注意です(coela)

This episode is about the pathophysiology on crystallopathies. The cellular pathways involved unify multiple concepts and multiple branches of medicine, from toxicology to cardiology to rheumatology and oncology. Heme Review YouTube Channel: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA References: [0] Crystallopathies. N Engl J Med 2016; 374:2465-2476. https://www.nejm.org/doi/full/10.1056/NEJMra1601611 [1] Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death & Disease. Volume 10, Article number: 128 (2019). https://www.nature.com/articles/s41419-019-1413-8 [2] The Inflammasome. Molecular Cell. VOLUME 10, ISSUE 2, P417-426, AUGUST 01, 2002. https://www.cell.com/molecular-cell/fulltext/S1097-2765(02)00599-3 [3] Silica crystals and aluminum salts mediate NALP-3 inflammasome activation via phagosomal destabilization. Nat Immunol. 2008 Aug; 9(8): 847–856. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834784/ [4] Tumor Cell–Derived IL1β Promotes Desmoplasia and Immune Suppression in Pancreatic Cancer. Cancer Res 2020;80:1088–101. https://cancerres.aacrjournals.org/content/80/5/1088 --- Support this podcast: https://anchor.fm/chubbyemu/support

改良型のCRISPR–Cas9によるゲノム編集ツールAFIDと変異パターンの予測について原著論文を紹介しました。Shownotes Precise, predictable multi-nucleotide deletions in rice and wheat using APOBEC–Cas9, Nature Biotechnology 2020…今回はこの論文を紹介しました。APOBEC–Cas9 fusion-induced deletion systems (AFIDs)と呼ばれるゲノム編集技術です。 Non-homologous end joining (NMEJ)…Cas9で誘導される二本鎖DNA切断が修復される仕組みの一つ。 Researchat.fmで話した過去のCas9関連エピソード…これまでにep2、ep22、ep31などでCas9やゲノム編集について話しています。 31. Editing the unedited, Researchat.fm…PrimeEditingと呼ばれるゲノム編集技術について原著論文を解説しました。 APOBEC3と病態：APOBEC3によるゲノム変異と発がん (Journal of Japanese Biochemical Society 88(5): 576-581 (2016))…今回の論文で使われているAPOBECについての詳しい日本語のレビュー論文です。 Uracil-DNA Glycosylase (UNG)…Cas9のC末端に融合されたタンパク質の一つ。分子生物学の実験に使われたりしています。 AP site (apurinic/apyrimidinic site) (Wikipedia)…核酸塩基が抜けた部位のこと。ウラシルはUDGによってAP siteになることが知られています。 Base excision repair (BER) (Wikipedia)…DNA修復の重要なパスウェイの一つ。APOBECによって変換されたウラシルはこのパスウェイによって修復される。 DNA Repair Profiling Reveals Nonrandom Outcomes at Cas9-Mediated Breaks. Molecular Cell, 2016…Cas9によって引き起こされる欠失変異のパターンはランダムではない、ということを始めて報告した論文。 Predictable and precise template-free CRISPR editing of pathogenic variants. Nature, 2018…大量のゲノム編集アッセイによってゲノム編集のパターンを計測し、そこから機械学習モデルを作成することで、ゲノム編集パターンの予測に成功した最初の論文。 Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9 … MMEJのpathwayを利用したゲノム編集 29歳独身中堅冒険者の日常 (マンガ)…今回紹介したcoelaのおすすめマンガ。 Editorial notes いい加減Tamakiさん紹介のマンガでも読むか… (soh) CRISPRシステムが受精直後の受精卵でも働く理由が気になっている。受精直後の卵でそもそもDNA修復経路が働いている理由とは…???(tadasu) マンガとかアニメのキャラより年齢が上になってきた…やはり悟空は偉大(coela)

Dr. Azra Raza is the Chan Soon-Shiong Professor of Medicine and Director of the MDS Center at Columbia University in New York. She is considered an international authority on pre-leukemia (MDS) and acute leukemia and is one of those rare physician-scientists who divide their time equally between caring for patients and supervising a state-of-the-art basic research lab which is well-funded by multiple large grants. Dr. Raza started collecting blood and marrow samples on her patients in 1984 and now her Tissue Bank, the largest and oldest in the country with >60,000 samples, is considered a unique national treasure. Dr. Raza has published her original clinical and basic research comprising over 300 peer-reviewed manuscripts in high profile journals like Nature, New England Journal of Medicine, Cell, Molecular Cell, Cancer Research, Blood, Leukemia. She is the author of The First Cell: And the Human Costs of Pursuing Cancer to the Last published October 2019.

V seriji predstavitev letošnjih prejemnikov Zoisovih nagrad in priznanj vas vabimo, da ponovno prisluhnete pogovoru z molekularnim biologom prof. dr. Borisom Rogljem, ki je za pomembne dosežke pri raziskavah molekularnih osnov nevrodegeneracije letos prejel Zoisovo priznanje. Pogovor s prof. Rogljem je nastal ob odmevni raziskavi, objavljeni letos spomladi v ugledni reviji Molecular Cell, v kateri je skupini slovenskih znanstvenikov uspelo razkriti mehanizme, ki pripeljejo do diferenciacije matičnih celic. Izkazalo se je tudi, da so v teh najzgodnejših procesih v življenju celic na delu procesi, ki vplivajo tudi na njihovo propadanje, kot ga srečamo pri nevrodegenerativnih boleznih.

Onderzoekers uit Pittsburgh (VS) zijn er voor het eerst in geslaagd om enkel schade te veroorzaken in de telomeren, de uiteinden van de chromosomen die een beschermlaagje vormen voor de rest van het DNA. Telomeren spelen een zeer belangrijke rol bij de veroudering van de cel. Per deling worden de telomeren telkens een stukje dunner, waardoor celdeling uiteindelijk stopt, de cel te oud is geworden om te functioneren en doodgaat. Dat lijkt nadelig, maar het mechanisme beschermt ons wel tegen kanker, omdat kankercellen wel onbeperkt kunnen delen. Maar oxidatieve stress (zuurstofradicalen die vrijkomen bij onze ademhaling en in extra hoeveelheden in het lichaam kunnen ontstaan door o.a. roken, alcoholgebruik, obesitas en ontstekingen) beschadigt het DNA in onze cellen en kan kanker veroorzaken of celveroudering bevorderen. Onderzoekers hadden altijd een vermoeden dat DNA-schade aan de telomeren daaraan kan bijdragen. Maar dat was nog niet eerder aangetoond, omdat het technisch niet mogelijk was om alleen de telomeren en niet de rest van het DNA te beschadigen. Met een nieuwe techniek konden de Amerikaanse onderzoekers het deze keer wel bewijzen. De gevolgen van de schade van zo'n telomeren-crisis zijn niet min. De cel kan stoppen met delen en sterven, of (als de cel het overleeft) kankerverwekkende eigenschappen krijgen doordat het voortdurend blijft delen. De onderzoekers publiceerden hun bevindingen in het wetenschappelijke tijdschrift Molecular Cell. Voor Jan Hoeijmakers, moleculair geneticus aan het Erasmus MC, zijn de bevindingen van het onderzoek en de nieuwe techniek van grote waarde in de strijd tegen ziektes zoals kanker, en veroudering. We horen van hem waarom dat zo is. Hoeijmakers publiceerde eerder een Nature-studie waaruit blijkt dat verminderd eten bij muizen voor minder oxidatieve stress zorgt.

V drobnih, očem nevidnih celicah poteka izredno zapleteno dogajanje. Tam kompleksne biološke molekule izmenjujejo informacije, prenašajo ukaze, izdelujejo nove kompleksne molekule in tvorijo temelj življenja. Kaj vse se v celicah dogaja, je predmet intenzivnih raziskav. Tudi v želji, da bi se tako pojasnilo in ozdravilo marsikatero bolezen. Molekularni biolog dr. Boris Rogelj z odseka za biotehnologijo na Institutu »Jožef Stefan« in redni profesor na Fakulteti za kemijo in kemijsko tehnologijo Univerze v Ljubljani se v prvi vrsti posveča raziskovanju procesov, ki se skrivajo v ozadju nevrodegenerativnih bolezni. Pred nekaj leti je prišel na sled enemu od genskih vzrokov, ki lahko pripeljejo do nastanka amiotrofične lateralne skleroze, poznane tudi pod kratico ALS. Toda "krivec" ima mnogo bolj večplastno vlogo, kot bi nemara domnevali na prvi pogled. To se je pokazalo v raziskavi, objavljeni v znanstveni reviji Molecular Cell, v kateri so s sodelavci prvič uspešno opisali celično regulativno mrežo, ki pojasnjuje prve razvojne dogodke, ki vodijo v učinkovito diferenciacijo matičnih celic in razvoj zarodka. Presenetljivo se je pokazalo, da je tako pri diferenciaciji matičnih celic kot tudi pri nastanku nevrodegenerativnih bolezni na delu isti protein TDP 43.

Our newest co-host has already had a taste of fame. Abby Fyfe joins the crew this time, along with Aline Sandouk, Jayden Bowen, and Aditi Patel. Turns out, Abby is an old hand at being internet famous, because she was once run over by a bus. True story. She has since regained her 3-dimensional shape, but did she mine that experience for her med school applications? But first, listener Tyler wants to know: is your undergrad institution's reputation an important factor for med school admissions committees? And we got some feedback from Alex, an actual registered dietician, and Blake responds to a recent question from Courtney about raising kids during med school. Later, Jayden quizzes us: can we guess what these genes do based on their very geeky names?In light of recent scandals in research and retractions of studies, an article in Molecular Cell proposes a Hippocratic Oath for scientists. And there's a new opioid possibly coming to market that is 500 times more powerful than morphine. What experiences did you mine for your med school application? Call us at 347-SHORTCT anytime, visit our Facebook group, or email theshortcoats@gmail.com. Do all three!

Chromatin Immunoprecipitation (ChIP) was first developed in Drosophila, where interactions of RNA Pol II with genes were investigated (Mol. Cell. Biol. August 1985 vol. 5 no. 8 2009-2018). Then, in a 1993 publication, (Genes & Dev. 1993 7:592-604), the group of James Broach described the association of histone acetylation state with transcriptional gene silencing in yeast. The technique was first used successfully in mammalian cells by Richard Treisman's group, published in 1998 (Cell (1998) 92:475-87).Chromatin Immunoprecipitation is used to link specific states of chromatin to individual loci in a cell, to understand how genes are regulated, and to decipher the Histone Code. In this Episode, we discuss the multiple challenges of ChIP experiments and the difficulties that can arise during different steps of the process. References for this episode Epigenetics News: Chung-Chau Hon, Jordan A. Ramilowski, … Alistair R. R. Forrest. An atlas of human long non-coding RNAs with accurate 5′ ends. Nature. March 2017. doi:10.1038/nature21374 Jennifer L. Guerriero, Alaba Sotayo, … Anthony Letai. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. March 2017. doi:10.1038/nature21409 Nitika Taneja, Martin Zofall, … Shiv I. S. Grewal. SNF2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance and Proper Replication. Molecular Cell. April 2017. DOI:10.1016/j.molcel.2017.02.006 Multiple Challenges in ChIP D. S. Gilmour, J. T. Lis. In vivo interactions of RNA polymerase II with genes of Drosophila melanogaster. Molecular and Cellular Biology. August 1985. doi:10.1128/MCB.5.8.2009 M. Braunstein, A. B. Rose, … J. R. Broach. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes & Development. 1993. doi:10.1101/gad.7.4.592 Arthur S. Alberts, Olivier Geneste, Richard Treisman. Activation of SRF-Regulated Chromosomal Templates by Rho-Family GTPases Requires a Signal that Also Induces H4 Hyperacetylation. Cell. February 1986. doi:10.1016/S0092-8674(00)80941-1 Active Motif Contact Details Follow us on Twitter Join us on LinkedIn Like us on Facebook Email us @Active Motif Europe or Active Motif North America.

2017-04-24 Special EnglishThis is Special English. I'm Mark Griffiths in Beijing. Here is the news.Beijing has put a new medical care reform plan into effect, bringing an end to medicine price markups.More than 3,600 medical institutions are involved in the reform and all of them have abolished the medicine price markups. That's according to the Beijing Municipal Commission of Health and Family Planning.It is estimated that the cost of treatment per outpatient will be reduced by around 5 percent on average thanks to cuts in medicine prices. There will be an average cost increase of 2.5 percent for inpatient treatment due to the growth of certain service charges.Community hospitals and medical institutions have been given the same access to the medicines usually prescribed in higher-level hospitals, so that patients can have more choices.Marking up medicine prices is a practice that has been adopted by most public hospitals in China since the 1950s. It allows hospitals to sell drugs with markups usually at a rate of 15 percent above the drugs' tag prices.The reform aims to effectively motivate medical staff to pay more attention to the medical service they are providing, and further improve the doctor-patient relationship.This is Special English.China has launched its largest operation to control air pollution in the northern regions. The operation has sent more than 5,600 inspectors to push the areas to meet ambitious pollution reduction targets.Unlike the nationwide inspections conducted last year, the yearlong, intensified inspection is being led by the Ministry of Environmental Protection.The inspectors will keep a spotlight on governments and companies in 28 major cities which are susceptible to heavy smog.Inspectors will check important areas including governments' implementation of air pollution control efforts. They will also shut down small plants with high emissions.Through the inspection, the ministry will push the governments and companies to fully implement measures to tackle air pollution.The ministry will closely watch the regions with pollution problems and stick with them until all the pollution issues are resolved.During a separate inspection, officials checked 450 companies and government departments. The inspection team found 280 violations, including companies that falsified monitoring data or discharged excessive pollutants.You're listening to Special English. I'm Mark Griffiths in Beijing.A recent cooperation deal between China and Kenya has become an important step for China's nuclear power technology to go global. The China General Nuclear Power Corporation announced recently that the company has signed a nuclear power training cooperation framework agreement with the Kenya Nuclear Electricity Board.Under the deal, China's Hualong One reactor is expected to be applied in Africa.The 1,000-megawatt water reactor was developed by the China General Nuclear Power Corporation and the China National Nuclear Corporation. It has reached the highest international safety standards to prevent leakage of radioactive materials and resist earthquakes.The China General Nuclear Power Corporation has formed a joint venture with Electricite de France SA to develop the Bradwell nuclear power plant in the UK, as well as to fund and design the reactor.The British government started an assessment of the reactor design in January. The process is expected to take around five years.Observers say there is a high possibility that the reactor design will pass the UK's approval process.This is Special English.Chinese scientists have extracted a medicinal compound from a natural herb called thunder god vine, which targets cell metabolism and could help tackle obesity.Celastrol, extracted from thunder god vine, and artemisinin, developed from sweet wormwood, are among five herbal compounds believed to have the most potential to treat illnesses where no cure has been discovered, including cancer.The discovery of artemisinin won Chinese scientist Tu Youyou a Nobel Prize in 2015.The research team was led by Zhang Xiaokun, professor with the College of Medicine at Xiamen University. It found that celastrol from the thunder god vine can alleviate inflammation.The team carried out the research on mice. The study found that celastrol could effectively control weight increases in mice feeding on high fat food.The research paper was published in science journal Molecular Cell on April 6.Scientists will continue to study how celastrol regulates metabolism to explore new drugs, with low toxicity and high efficiency, to help people lose weight.You're listening to Special English. I'm Mark Griffiths in Beijing. The Chinese Academy of Sciences has earmarked 10 million yuan, roughly 1.4 million U.S. dollars, for the research and development of an advanced artificial intelligence processor.The deep learning processor chip, the "Cambrian", is expected to become the world's first processor that simulates human nerve cells to conduct deep learning.The program is named after the Cambrian Period, which marked a rapid diversification of life forms on earth. Scientists expect that the processor will spearhead a new era in artificial intelligence.The investment will be used in basic research areas to explore the structure and algorithm for the next generation of artificial intelligence. The project also aims to lay a foundation for China's ambition in the global chip market.The funds will also be used to promote and publicize the research.Google's artificial intelligence program AlphaGo needs huge power and large servers to operate. The Cambrian aims to perform at the same level but using only one watt of power. The processor will have the size of a smartphone or a watch.This is Special English.Industry insiders say the planned Xiong-an New Area in Hebei province is expected to bring tourism opportunities to a large wetland area and to the province as a whole.China announced a decision to set up the new area to boost coordinated development of Beijing, Tianjin and Hebei province.Over the following three days, during the Tomb Sweeping Day holiday, the Baiyangdian Lake tourist area received 18,000 visitors. Tourism income reached 16 million yuan, roughly 2.4 million US dollars. Both figures represented a 260 percent increase compared with last year.The lake is one of North China's largest freshwater wetlands. It is located in Anxin County, which is part of the new area.An online travel service provider said the new area has the basic infrastructure for attracting tourists. It has adequate tourism resources and easy transport. The plan of the new area has attracted the attention of people from across the country to go for a visit.Bookings on the website during the holiday tripled that of last year. Tourists mainly came from neighboring Beijing and Shandong province. There are also people from farther afield, including Shanghai and Guangdong Province.You're listening to Special English. I'm Mark Griffiths in Beijing. You can access the program by logging on to crienglish.com. You can also find us on our Apple Podcast. Now the news continues.A woman from the Philippines has become the first person to receive a residence permit designed for foreigners providing housekeeping service in Shanghai. The event occurred in Shanghai's Pudong district, which houses more than 300 Fortune 500 companies and is home to the Pilot Free Trade Zone in the country.Liu Chen is a Chinese American and president of the Shanghai Affinity Biopharmaceutical Company. Liu applied for the one-year residence permit on March 14 for the housemaid he hired. Two weeks later, she obtained the permit.More than 20 foreign housemaids have received their residence permits in Shanghai. Liu's was the only case that has been made public.The permission for foreign housemaids is one of the measures Shanghai has unveiled since July 2015 to attract talented foreigners as the city tries to build itself into a global technological innovation hub by 2030.This is Special English.Education experts say Children should have more opportunities to participate in study tours or other outdoor activities only if their safety is guaranteed.In developed countries, including the United States and Japan, study tours such as summer camps are key activities and are always the source of unforgettable memories. That's according to Sun Yunxiao, chief expert of the China Youth and Children Research Center. Sun says that in China, young people are having less opportunity to enjoy such activities because schools and parents are cutting down on them for security concerns.In recent years, accidents in which children were killed or injured while participating in school outdoor activities have been reported by the media. The events raised concerns among parents. A vice chairman of the Chinese Society of Education said a test-oriented education is also part of the reason for the shrinking number of study tours.Another expert says student workloads are heavy, leaving them little time for traveling.In December, 11 ministries in China jointly released a guideline, stating that study tours will become part of the curriculum system in primary and middle schools nationwide.You're listening to Special English. I'm Mark Griffiths in Beijing. A new system is being introduced in southern China's Guangdong that gives parents and students more of a say over the designs of school uniforms.The move was put forward in a document jointly published by the province's education department, the industry and commerce administration, as well as the quality and technology administration.Manufacturers will be invited to showcase their wares in schools, but the final decision on which uniform should be adopted will be decided by a poll.Students and parents can also offer suggestions on how manufacturers can further improve their designs and the materials used for the uniforms.The price, design and materials used in school uniforms are decided by local education departments alone. The new plan allows different schools to have different styles of uniform.This is Special English.Macao has officially started its application for a member of the UNESCO Creative Cities Network as a City of Gastronomy.Macao has officially applied to become one of the most popular choices for food and restaurants, which will add another reputation to the city.Macao's Tourism Office listed the application as one of four major goals in 2017. It even set up a special committee in charge of the issue.Officials say that if Macao is successfully designated as a UNESCO gastronomy city, it will add a significant international brand for Macao with far-reaching significance. It will also serve as a powerful impetus to the sustainable development of Macao's economy.Macao held an "International Gastronomy Forum" in November as a warm-up before it officially applies for the branding.This is Special English.Spanning 1,100 meters across a river in southwest China's Sichuan Province, a main cable backstay bridge has been successfully installed. The bridge, on the Luding River, is part of an expressway linking two cities in the province.This is the first suspension bridge in the province that has been built in a highly active seismic zone with complicated wind field and a large span. Around 34,000 steel cables will be used in the construction. The total length will reach 60,000 kilometers if all the cables are laid together in a single line, which is equivalent to 1.5 times of the circumference of the earth.The bridge has dual carriage way with four lanes of traffic in each direction, allowing vehicles to travel at 80 kilometers per hour.A drone was also used during the construction of the bridge.（全文见周六微信。）

In this edition, we learn how HIV is linked to premature aging, with Trey Ideker, Molecular Cell (00:00); how seeing and perceiving visual information isn’t actually the same thing, with Michael Cohen, Trends in Cognitive Sciences (7:48); how ancient trees need special conservation, with William Laurance, Trends in Ecology and Evolution (13:10); and how the salary gap persists between men and women (19:10). Plus much more!

In this edition, we’ll learn about how new tools for genetic editing are transforming the study of biology, with Jennifer Doudna (00:00 Molecular Cell), how the female body may ‘remember’ pregnancy, with Gregory Hannon (8:20 Cell Reports) and how to train your neuroscientist, with Brian Litt (14:20 Neuron) and a round-up of great science stories from Cell Press this month! (22:18). 

Cancer is an unwanted experiment in progress. As the disease advances, tumor cells accumulate mutations, eventually arriving at ones that give them the insidious power to grow uncontrollably and spread. A study led by Jared Rutter, Ph.D., professor of biochemistry at the University of Utah, reports that cancers select against a protein complex called the mitochondrial pyruvate carrier (MPC), and re-introduction of MPC in colon cancer cells impairs several properties of cancer, including growth. The research appeared online on Oct. 30 in Molecular Cell. Rutter explains how the work implicates changes in a key step in metabolism – the way cellular fuel is utilized – as an important driver of cancer, and how the findings may be exploited to develop new cancer therapies.

Richard Cogdell is the Director of the Institute for Molecular Cell and Systems Biology at the University of Glasglow, Scotland. Richard was led to a career in studying bacterial photosynthesis by a desire to learn and understand basic photosynthesis, he "wanted to know how natured worked." In 1995, Richard's research group, in collaboration with others, used protein crystallography to determine the three dimensional structure of a light-harvesting complex from the purple bacterium, Rhodospsedomas acidophilia. This breakthrough led to two key elements in the understanding of bacterial photosynthesis. One, once you have established the structure you can understand its function. Two, this view of a light-harvesting complex attracted an interdisciplinary group of scientists from the fields such as chemistry, physics, mathematics and biology. Richard's current challenge is to take the process of photosynthesis (using solar energy to make a fuel) and apply it to the world's energy needs in a sustainable manner. To do this, Richard says "you must break photosynthesis down to it's four most basics steps", absorb solar energy, concentrate it, break it apart and make a fuel. These are the steps that must be duplicated if they are going to be successful at creating sustainable, renewable energy. The first two steps, says Cogdell, are like a solar battery (easy to recreate). The hard part is finding ways to use renewable energy to drive the chemistry. That's the process Richard spends most of his time working on and he uses the concept of an artificial leaf to help explain this complex process to the public. According to Cogdell, if the current rate of investment continues, it will be approximately five to six years before we see a small pilot system that demonstrates the feasibility of the process. Richard emphasizes that if mankind wants to survive, we must find a way to convert solar energy into fuel because when fossil fuels run out so do we.

Richard Cogdell is the Director of the Institute for Molecular Cell and Systems Biology at the University of Glasglow, Scotland. Richard was led to a career in studying bacterial photosynthesis by a desire to learn and understand basic photosynthesis, he "wanted to know how natured worked." In 1995, Richard's research group, in collaboration with others, used protein crystallography to determine the three dimensional structure of a light-harvesting complex from the purple bacterium, Rhodospsedomas acidophilia. This breakthrough led to two key elements in the understanding of bacterial photosynthesis. One, once you have established the structure you can understand its function. Two, this view of a light-harvesting complex attracted an interdisciplinary group of scientists from the fields such as chemistry, physics, mathematics and biology. Richard's current challenge is to take the process of photosynthesis (using solar energy to make a fuel) and apply it to the world's energy needs in a sustainable manner. To do this, Richard says "you must break photosynthesis down to it's four most basics steps", absorb solar energy, concentrate it, break it apart and make a fuel. These are the steps that must be duplicated if they are going to be successful at creating sustainable, renewable energy. The first two steps, says Cogdell, are like a solar battery (easy to recreate). The hard part is finding ways to use renewable energy to drive the chemistry. That's the process Richard spends most of his time working on and he uses the concept of an artificial leaf to help explain this complex process to the public. According to Cogdell, if the current rate of investment continues, it will be approximately five to six years before we see a small pilot system that demonstrates the feasibility of the process. Richard emphasizes that if mankind wants to survive, we must find a way to convert solar energy into fuel because when fossil fuels run out so do we.

Richard Cogdell is the Director of the Institute for Molecular Cell and Systems Biology at the University of Glasglow, Scotland. Richard was led to a career in studying bacterial photosynthesis by a desire to learn and understand basic photosynthesis, he "wanted to know how natured worked." In 1995, Richard's research group, in collaboration with others, used protein crystallography to determine the three dimensional structure of a light-harvesting complex from the purple bacterium, Rhodospsedomas acidophilia. This breakthrough led to two key elements in the understanding of bacterial photosynthesis. One, once you have established the structure you can understand its function. Two, this view of a light-harvesting complex attracted an interdisciplinary group of scientists from the fields such as chemistry, physics, mathematics and biology. Richard's current challenge is to take the process of photosynthesis (using solar energy to make a fuel) and apply it to the world's energy needs in a sustainable manner. To do this, Richard says "you must break photosynthesis down to it's four most basics steps", absorb solar energy, concentrate it, break it apart and make a fuel. These are the steps that must be duplicated if they are going to be successful at creating sustainable, renewable energy. The first two steps, says Cogdell, are like a solar battery (easy to recreate). The hard part is finding ways to use renewable energy to drive the chemistry. That's the process Richard spends most of his time working on and he uses the concept of an artificial leaf to help explain this complex process to the public. According to Cogdell, if the current rate of investment continues, it will be approximately five to six years before we see a small pilot system that demonstrates the feasibility of the process. Richard emphasizes that if mankind wants to survive, we must find a way to convert solar energy into fuel because when fossil fuels run out so do we.

How understanding neural control of appetite might help fight obesity, with Tamas Horvath (0:00) Trends in Neurosciences. How elemental design principles can provide insight into biological processing, with Wendell Lim (8:42) Molecular Cell. Plus, sample a selection of the hottest new papers from Cell Press (16:12).