{
  "abstract": "The human genome is thought to contain 100s of thousands of enhancers with, as yet, uncharacterised activities and a large proportion of disease-causing and disease-predisposing DNA sequence variants map to potential enhancers. To advance understanding of human disease, massive efforts are currently being directed towards establishing genotype to phenotype correlations for sequence variants. A key pre-requisite to these analyses is defining the precise cell- and tissue-specific activities of the enhancers, in a context that is relevant to the biology associated disease.Our research focuses on addressing this knowledge gap by building in vivo and ex vivo models for visualising and defining cell-type specific enhancer functions using an exemplar locus for enhancer- mediated gene regulation- PAX6, the master regulator of eye development. PAX6 has a regulatory landscape containing multiple enhancers driving expression in the eye. Whether these enhancers perform additive, redundant, or distinct functions is unknown.We have developed in vivo (zebrafish) and ex vivo (optic cup organoids) models enabling visualization of the precise spatial and temporal roles of PAX6 enhancers in the developing eye. Using a combination of high-resolution live imaging, single cell RNA- sequencing and synthetic biology approaches in these model systems we have uncovered cell type specific regulatory activities of enhancers at single-cell resolution. Here I will present our most recent work revealing enhancer usage dynamics during zebrafish embryonic development at cell-type specific resolution in a fully synthetic complete PAX6 regulatory domain integrated in the zebrafish genome.",
  "authors": [
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Shipra Bhatia"
    },
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Grace Alston"
    },
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Anita Mann"
    },
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Xinhao Hou"
    },
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Kirsty Uttley"
    },
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Alba Gonzalez Estevez"
    },
    {
      "affiliations": [
        "Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY 10016, USA"
      ],
      "name": "Brianna Berrios"
    },
    {
      "affiliations": [
        "Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY 10016, USA"
      ],
      "name": "Jef D Boeke"
    },
    {
      "affiliations": [
        "MRC Human Genetics Unit, Institute of Genetics and Cancer, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK"
      ],
      "name": "Wendy A Bickmore"
    }
  ],
  "title": "#ECR-Poster-06 Investigating complex gene regulatory landscapes in eye development using synthetic biology and single cell-RNA sequencing",
  "uid": "ff47f740-5448-58a5-8bc5-420dd23eb622"
}