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SUMMARY:Converging on Cancer: International Seminar Series – Prof Fran Su
 pek (BRIC – Copenhagen) and Dr Syed Haider (ICR)
DESCRIPTION:The CRUK Convergence Science Centre is a partnership between Im
 perial College London and The Institute of Cancer Research. In collaborati
 on with our international partners we arrange a regular international semi
 nar ‘Converging on Cancer’ on the topic of interdisciplinary cancer re
 search. Our partners are:\n\nTechnical University of Munich (TUM)\nNanyang
  Technological University (NTU)\nBiotech Research and Innovation Centre (B
 RIC – University of Copenhagen)\nÉcole Polytechnique Fédérale de Laus
 anne (EPFL).\n\n\nIn this series\, we bring together speakers from across 
 these institutions to present their research and how they use convergence 
 science to answer cancer-related questions. This seminar will focus on ide
 ntifying cancer vulnerabilities through novel genomics approaches.\n \nTh
 ursday 2nd July\, 10-11am BST\, 11-12pm CEST\, 5-6pm SGT\n\nSpeakers\nProf
  Fran Supek (BRIC\, Copenhagen) \nModelling mutational mechanisms in canc
 er genomes using isogenic cells generated via combinatorial gene editing\n
 Mismatch repair deficiency is usually treated as a binary cancer phenotype
  — MSI-high or not — but whole-genome data suggest a richer landscape 
 of MMR failure. In this seminar\, Fran Supek will present a combinatorial 
 CRISPR/Cas12a mutation-accumulation study in human cells showing that diff
 erent MMR and BER gene defects generate distinct and reproducible mutation
 al spectra of SNVs\, indels\, and microsatellite alterations. We identify 
 genome-wide patterns of MSH3-driven EMAST\, PMS2- and MSH6-specific mutati
 onal states\, and show that experimentally defined repair-defect signature
 s can be reliably recognized in cancer genomes. Together\, the study refra
 mes MSI as a multidimensional evolutionary phenotype shaped by DNA repair 
 genotype and pathway interactions.\n \nDr Syed Haider (ICR)\nSystematic i
 n silico discovery and modelling of cancer-associated synthetic lethal int
 eractions\nTo maintain cell fitness\, deleterious genetic alterations are 
 buffered by compensatory changes in additional genes. In cancer\, bufferin
 g processes could be targeted by synthetic lethality. However\, despite th
 e large-scale identification of synthetic lethal effects in preclinical mo
 dels\, evidence that these operate clinically is limited. This impedes the
  application of synthetic lethal approaches. By integrating molecular prof
 iling data from >9\,000 cancers with synthetic lethal screens\, we show th
 at transcriptomic buffering of tumor suppressor gene (TSG) loss by hyperex
 pression of synthetic lethal partners is a common phenomenon\, extending t
 o multiple TSGs and histotypes. We further show that by integrating hypere
 xpression along with the evolutionary information on paralogous genes\, gi
 ven that paralogs often provide buffering against the loss of fitness caus
 ed by loss of one paralog\, can be further exploited to identify higher-or
 der polygenic synthetic lethal interactions in human cancers.\n\n \n\nWho
  can attend?\nResearchers\, students and anyone with an interest in conver
 gence science relating to cancer research across our partnered institutio
 ns are welcome to register:\n\nCRUK Convergence Science Centre\nImperial 
 College London\nThe Institute of Cancer Research (ICR)\nTechnical Universi
 ty of Munich (TUM)\nNanyang Technological University (NTU)\nBiotech Resear
 ch and Innovation Centre (BRIC – University of Copenhagen)\nÉcole Polyt
 echnique Fédérale de Lausanne (EPFL)\nCRUK Cambridge Centre\nCRUK City o
 f London Centre (Kings college\, UCL\, Barts Cancer Institute/Queen Mary U
 niversity\, Francis Crick)\nCRUK Manchester Centre\nCRUK Newcastle Centre\
 nCRUK Oxford Centre\nCRUK Scotland Centre (University of Edinburgh and Uni
 versity of Glasgow)\n\n \nEmail icr-imperial-convergence.centre@imperial.
 ac.uk to receive the registration link and joining details.\n 
URL:https://www.imperial.ac.uk/events/210676/converging-on-cancer-internati
 onal-seminar-series-prof-fran-supek-bric-copenhagen-and-dr-syed-haider-icr
 /
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LOCATION:United Kingdom
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