New tools for functional imaging of the intestinal organoids

About this line of research

Adult stem cells and iPSC-derived intestinal organoids advance our understanding of intestinal epithelium development, host-microbe interaction studies and tissue engineering applications. Recent research underlines the importance of high-resolution and live microscopy approaches for better understanding organoid heterogeneity and metabolism. We pioneered FLIM and O2 PLIM imaging of organoids by addressing their oxidative metabolism and currently expanding the available biosensor toolkit for improved multi-factor assessment of single-cell metabolism and fate in the organoids via non-invasive live and multi-parameter FLIM microscopy.

The consolidation of these approaches will enable for deeper understanding of the tissue healing process in patients with inflammatory bowel disease (IBD), produce improved modelling of host-microbe interactions and reveal the role of dietary iron in intestinal cell homeostasis.

Publications

  1. Okkelman IA, Neto N, Papkovsky DB, Monaghan MG, Dmitriev RI: A deeper understanding of intestinal organoid metabolism revealed by combining fluorescence lifetime imaging microscopy (FLIM) and extracellular flux analyses. Redox Biology 2020, 30:101420.
  2. Okkelman IA, McGarrigle R, O’Carroll S, Berrio DC, Schenke-Layland K, Hynes J, Dmitriev RI: Extracellular Ca2+-Sensing Fluorescent Protein Biosensor Based on a Collagen-Binding Domain. ACS Applied Bio Materials 2020, 3(8):5310-5321.
  3. Okkelman IA, Foley T, Papkovsky DB, Dmitriev RI: Live cell imaging of mouse intestinal organoids reveals heterogeneity in their oxygenation. Biomaterials 2017, 146:86-96.
  4. O'Donnell N, Okkelman IA, Timashev P, Gromovykh TI, Papkovsky DB, Dmitriev RI: Cellulose-based scaffolds for fluorescence lifetime imaging-assisted tissue engineering. Acta Biomaterialia 2018, 80:85-96.

Questions?

  • Ruslan Dmitriev, professor/head of the group

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