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Träfflista för sökning "WFRF:(Rajakumar Timothy) "

Search: WFRF:(Rajakumar Timothy)

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  • Bassett, Andrew R., et al. (author)
  • Understanding functional miRNA-target interactions in vivo by site-specific genome engineering
  • 2014
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4640-
  • Journal article (peer-reviewed)abstract
    • MicroRNA (miRNA) target recognition is largely dictated by short 'seed' sequences, and single miRNAs therefore have the potential to regulate a large number of genes. Understanding the contribution of specific miRNA-target interactions to the regulation of biological processes in vivo remains challenging. Here we use transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technologies to interrogate the functional relevance of predicted miRNA response elements (MREs) to post-transcriptional silencing in zebrafish and Drosophila. We also demonstrate an effective strategy that uses CRISPR-mediated homology-directed repair with short oligonucleotide donors for the assessment of MRE activity in human cells. These methods facilitate analysis of the direct phenotypic consequences resulting from blocking specific miRNA-MRE interactions at any point during development.
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2.
  • Erickson, Andrew, et al. (author)
  • The spatial landscape of clonal somatic mutations in benign and malignant tissue
  • Other publication (other academic/artistic)abstract
    • Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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  • Result 1-3 of 3

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