The CRUK Convergence Science Centre is a partnership between 911½ñÈÕºÚÁÏ and The Institute of Cancer Research. In collaboration with our international partners we arrange a regular international seminar ‘Converging on Cancer’ on the topic of interdisciplinary cancer research. Our partners are:
- Technical University of Munich (TUM)
- Nanyang Technological University (NTU)
- Biotech Research and Innovation Centre (BRIC – University of Copenhagen)
- École Polytechnique Fédérale de Lausanne (EPFL).
In 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 identifying cancer vulnerabilities through novel genomics approaches.
Ìý
Thursday 2nd July, 10-11am BST, 11-12pm CEST, 5-6pm SGT
Speakers
Ìý
Modelling mutational mechanisms in cancer genomes using isogenic cells generated via combinatorial gene editing
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 different MMR and BER gene defects generate distinct and reproducible mutational spectra of SNVs, indels, and microsatellite alterations. We identify genome-wide patterns of MSH3-driven EMAST, PMS2- and MSH6-specific mutational states, and show that experimentally defined repair-defect signatures can be reliably recognized in cancer genomes. Together, the study reframes MSI as a multidimensional evolutionary phenotype shaped by DNA repair genotype and pathway interactions.
Ìý
Systematic in silico discovery and modelling of cancer-associated synthetic lethal interactions
To maintain cell fitness, deleterious genetic alterations are buffered by compensatory changes in additional genes. In cancer, buffering processes could be targeted by synthetic lethality. However, despite the large-scale identification of synthetic lethal effects in preclinical models, evidence that these operate clinically is limited. This impedes the application of synthetic lethal approaches. By integrating molecular profiling data from >9,000 cancers with synthetic lethal screens, we show that transcriptomic buffering of tumor suppressor gene (TSG) loss by hyperexpression of synthetic lethal partners is a common phenomenon, extending to multiple TSGs and histotypes. We further show that by integrating hyperexpression along with the evolutionary information on paralogous genes, given that paralogs often provide buffering against the loss of fitness caused by loss of one paralog, can be further exploited to identify higher-order polygenic synthetic lethal interactions in human cancers.
Ìý
Who can attend?
Researchers, students and anyone with an interest in convergence science relating to cancer researchÌýacross our partnered institutionsÌýare welcome to register:
- CRUK Convergence Science Centre
- 911½ñÈÕºÚÁÏ
- The Institute of Cancer Research (ICR)
- Technical University of Munich (TUM)
- Nanyang Technological University (NTU)
- Biotech Research and Innovation Centre (BRIC – University of Copenhagen)
- École Polytechnique Fédérale de Lausanne (EPFL)
- CRUK Cambridge Centre
- CRUK City of London Centre (Kings college, UCL, Barts Cancer Institute/Queen Mary University, Francis Crick)
- CRUK Manchester Centre
- CRUK Newcastle Centre
- CRUK Oxford Centre
- CRUK Scotland Centre (University of Edinburgh and University of Glasgow)
Ìý
Email icr-imperial-convergence.centre@imperial.ac.uk to receive the registration link and joining details.
Ìý