Archive Page: Skarnes Group | Stem cell engineering

Archive Page: Skarnes Group | Stem cell engineering

Skarnes Group

The Skarnes Group left the Sanger Institute in 2017. This page is being maintained as a historical record of the work of the group and is no longer being updated. Bill Skarnes now leads a group at the Jackson Laboratory:
skarnes-group-5.jpgSanger Institute, Genome Research Limited

Our Research and Approach

The exploitation of mouse and human pluripotent stem cells to elucidate gene function has great potential for high-impact science and medicine. Not only can normal diploid stem cells be used as a model cell for basic cell biological processes, but they also have the capacity to differentiate into many different cell types in vitro. Furthermore, undifferentiated and differentiated cells can be grown in sufficient numbers to carry out genomic assays such as expression profiling, mass spectrometry and epigenetic profiling.

Thus, stem cells are an excellent model system to identify genes and genetic pathways required for basic cellular and developmental processes. Genetic resources, which support the investigation of mammalian gene function in a model cell, will significantly enhance our understanding of normal and variant mammalian gene products in health and disease.

The advent of site-specific nucleases and improved culture conditions now permits efficient engineering of human stem cells. In particular the CRISPR-Cas9 technology provides a facile and highly efficient tool for generating a range of alleles in cultured cells with little risk of off-target damage in human stem cells.

The Stem cell engineering group developed methods for the generation of homozygous knockouts and point mutations at scale. The team generated permanent distributable libraries of engineered mutations in human stem cells that will be coupled to focused phenotyping screens in cultured cells. Phenotypic data was compiled in an electronic encyclopedia of gene function and released to the community together with the mutant cell resource.

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Dr Bill Skarnes
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  • Off-target mutations are rare in Cas9-modified mice.

    Iyer V, Shen B, Zhang W, Hodgkins A, Keane T et al.

    Nature methods 2015;12;6;479

  • WGE: a CRISPR database for genome engineering.

    Hodgkins A, Farne A, Perera S, Grego T, Parry-Smith DJ et al.

    Bioinformatics (Oxford, England) 2015;31;18;3078-80

  • Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function.

    Yeung AT, Hale C, Xia J, Tate PH, Goulding D et al.

    Scientific reports 2015;5;8908

  • Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects.

    Shen B, Zhang W, Zhang J, Zhou J, Wang J et al.

    Nature methods 2014;11;4;399-402