{
  "abstract": "The nucleus is a dynamic organelle which responds to both intrinsic and extrinsic forces. Sensing and responding to forces (termed mechanosensing) is especially important in cardiomyocytes which are under constant mechanical load.The nuclear envelope separates the contents of the nucleus from the cytoplasm and is made up of the inner and outer nuclear membranes. Responses to force are mediated by proteins that line the nuclear membranes, namely the LINC (Linker of Nucleoskeleton and Cytoskeleton) complexes which couple the nuclear lamina underlying the inner nuclear membrane to the wider cytoskeleton.1 Dysfunction in LINC, lamina and nuclear envelope proteins have been implicated in cardiomyopathies and muscular dystrophies where aberrant nuclear morphology, rupture and DNA damage may contribute to pathophysiology. For example, a missense mutation in the inner nuclear membrane protein lem2 has been implicated in dilated cardiomyopathy.2 Studies of nuclear dynamics are often carried out in-vitro, requiring mechanical interventions to apply force to nuclei resulting in aberrant nuclear morphology and rupture. However, there is little understanding of how these dynamic changes in nuclear morphology progress under mechanical load in-vivo. Therefore, there is an unmet need for a novel imaging platform capable of simultaneous mounting, culture, and subcellular imaging of live intact mammalian hearts.In this work we demonstrate an ability to isolate intact, contractile embryonic mouse hearts at a range of developmental stages, utilising lightsheet microscopy we are able to image live at a high spatiotemporal resolution. Refinement of a robust post-processing pipeline is ongoing alongside timed imaging to enable high resolution 4D reconstructions of contracting embryonic mouse hearts. Further development of this platform will allow for deeper understanding of cardiomyocyte nuclear dynamics across timescales in both normal and disease conditionsReference Stroud MJ. Linker of nucleoskeleton and cytoskeleton complex proteins in cardiomyopathy. Biophys Rev. 2018.Jacob A Ross, Nathaly Arcos-Villacis, Edmund Battey, Cornelis Boogerd, Constanza Avalos Orellana, Emilie Marhuenda, Pamela Swiatlowska, Didier Hodzic, Fabrice Prin, Tim Mohun, Norman Catibog, Olga Tapia, Larry Gerace, Thomas Iskratsch, Ajay M Shah, Matthew J Stroud. Lem2 is essential for cardiac development by maintaining nuclear integrity. Cardiovascular Research August 2023;119(11).",
  "authors": [
    {
      "affiliations": [
        "BHF Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London"
      ],
      "name": "George Doherty"
    },
    {
      "affiliations": [
        "BHF Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London"
      ],
      "name": "Jacob A Ross"
    },
    {
      "affiliations": [
        "BHF Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London"
      ],
      "name": "Elisabeth Ehler"
    },
    {
      "affiliations": [
        "BHF Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College London"
      ],
      "name": "Matthew J Stroud"
    }
  ],
  "title": "P29  Elucidating spatiotemporal nuclear dynamics in 4D using state-of-the-art imaging in beating hearts",
  "uid": "f459107f-0be6-5393-9b1a-10790b4c7766"
}