BEGIN:VCALENDAR VERSION:2.0 PRODID:talks.ox.ac.uk BEGIN:VEVENT SUMMARY:Cancer Evolution Seminar Series (CESS) - Professor Sui Huang (Inst itute for Systems Biology)\, Dr Jean-Jacques Kupiec (Centre Cavaillès de l'Ecole Normale Supérieure - Paris) DTSTART;VALUE=DATE-TIME:20210506T160000 DTEND;VALUE=DATE-TIME:20210506T173000 UID:https://talks.ox.ac.uk/talks/id/e81f9de2-fbe7-4810-9055-081f2cd0a005/ DESCRIPTION:MODERATOR: Denis Noble\, CBE\, FRS\, FMedSci\, MAE\, Professor Emeritus\; Co-Director of Computational Physiology\, Department of Physio logy\, Anatomy\, and Genetics\, University of Oxford\n\nSPEAKERS\n\nSui Hu ang\, Professor\, Institute for Systems Biology\n\nSui Huang\, MD\, PhD\, obtained his doctorates in medicine and in molecular biology at the Univer sity of Zurich in 1995\, working interferon-g. After 12 years as postdocto ral fellow and faculty at Harvard Medical School in Boston\, where he stud ied cell fate decisions and tumor angiogenesis\, he was recruited to the University of Calgary in 2007 and worked alongside Stuart Kauffman on gene regulatory networks and cancer therapy (=exiting the cancer attractor) be fore joining the Institute for Systems Biology in Seattle in 2011. Sui Hua ng demonstrated that cell types are attractor states in high-dimensional g ene expression space\, and subsequently showed cell state instability prec eding cell fate decisions. His current laboratory at ISB combines single-c ell omics technologies and theory of non-linear dynamical systems to bette r understand non-genetic mechanisms of tumor progression and an intrinsic limitation of cancer treatment: cancer treatment so often backfires... \n \nTitle: Non-genetic plasticity and Lamarckian Dynamics of Tumor Progress ion: What does not make me\, makes me stronger”\n\nAbstract: The idea th at the genotype maps in a deterministic 1:1 fashion to phenotype has long dictated evolution biology\, as well as cancer biology. Accordingly\, canc er progression is driven by a somatic Darwinian evolution of cells that ac cumulate mutations and undergo selection. In reality\, the link between ge netic mutation and cancer is much looser. For\, one genome can produce tho usands of stable and inheritable phenotypes\, most prosaically manifest in the diversity of cell types of the metazoan body. A cell of a distinct ty pes sits at the bottom of the valleys in Waddington’s epigenetic landsca pe. This familiar picture is more than a metaphor because it explains phen otypic variability (“plasticity”) in the absence of genetic alteration s by grounding it in the mathematical principles of gene regulatory networ k dynamics. In this talk I will propose how the departure from the rigid 1 :1 genotype-to-phenotype mapping prompts us to rethink evolution\, notably somatic evolution of the neoplastic cell in the development of therapy re sistance. Theory and experiments that I will present suggest that treatmen t either kills the cell\, or if not\, will induce a stemness state in the non-killed (but stressed) cells\, and make them more resilient – manifes ting a symmetry-breaking bifurcation. Such treatment-induced resistance co rresponds to a Lamarckian scheme of tumor evolution (without genetic mutat ions). But it is perhaps more fittingly described with Nietzsche: “What does not kill me makes me stronger\n\nDr. Jean-Jacques Kupiec (Centre Cava illès de l'Ecole Normale Supérieure - Paris) \n\nDr. Kupiec\, proposed in 1983 a cell differentiation model b ased on stochastic gene expression. Since then\, he has developed this mod el and has published a series of articles and books on the subject.\n\nTit le: Stochastic gene expression\, cell differentiation and cancer\n\nAbstra ct: Cells associate to form multicellular living beings through\, on the o ne hand\, stochastic gene expression and\, on the other hand\, interaction s with their internal environment which stabilize them. This model allows for testable predictions that were verified. Notably\, it predicts a surge in gene expression variability preceding cell differentiation. Computer s imulation experiments show that\, in this frame\, a living being is an equ ilibrium state between the intrinsic variation of cells and their interact ion with the internal environment\, and that the cause of cancer is a dist urbance of this equilibrium.\n\nReferences:\n\nKupiec\, J.J. A probabilist theory for cell differentiation\, embryonic mortality and DNA C-value par adox. Spec. Sci. Technol. 6(5):471-478\, 1983. (Republished in 2020 in Org anisms: Journal of Biological Sciences\, vol. 4\, no. 1\, pp. 80-85.)\n\nK upiec J.-J. A Darwinian theory for the origin of cellular differentiation. Mol. Gen. Genetics. 255: 201-208\, 1997\n\nKupiec J.-J. The Origin of Ind ividuals. World Scientific Publishing. 2009.\n\nHeams T. Approche endodarw inienne de la variabilité intercellulaire de l'expression génétique\, 2 004 Thèse de doctorat sous la direction de J.-J. Kupiec - Paris\, Institu t national d'agronomie\n\nLaforge\, B. et al.\, 2005. Modeling embryogenes is and cancer: an approach based on an equilibrium between the autostabili zation of stochastic gene expression and the interdependance of cells for proliferation. Progress Biophys. Mol. Biol. 89: 93-120.\n\nRichard A et al . Single-Cell-Based Analysis Highlights a Surge in Cell-to-Cell Molecular Variability Preceding Irreversible Commitment in a Differentiation Process . PLoS Biol. 2016 Dec 27\;14(12):e1002585. doi:10.1371/journal.pbio.100258 5.\n\nMoussy A et al. Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic c ell fate commitment. PLoS Biol. 2017 Jul 27\;15(7):e2001867. doi: 10.1371/ journal.pbio.2001867\n\nZOOM LINK\n\nJoin Zoom Meeting: https://zoom.us/j/ 97829518235?pwd=aUNlNlZqSEJsR0VKYjhrZVF1UGQrUT09\n\nMeeting ID: 978 2951 8 235\nPasscode: 706286\n\nFind your local number: https://zoom.us/u/aWocSF8 y\nSpeakers:\nProfessor Sui Huang (Institute for Systems Biology)\, Dr Jea n-Jacques Kupiec (Centre Cavaillès de l'Ecole Normale Supérieure - Paris ) LOCATION:Zoom webinar TZID:Europe/London URL:https://talks.ox.ac.uk/talks/id/e81f9de2-fbe7-4810-9055-081f2cd0a005/ BEGIN:VALARM ACTION:display DESCRIPTION:Talk:Cancer Evolution Seminar Series (CESS) - Professor Sui Hu ang (Institute for Systems Biology)\, Dr Jean-Jacques Kupiec (Centre Cavai llès de l'Ecole Normale Supérieure - Paris) TRIGGER:-PT1H END:VALARM END:VEVENT END:VCALENDAR