A super-resolution optical microscope that images thicker, live tissue samples has been installed to study bowel development and inflammatory bowel disease; researchers say it will let them track molecular events inside cells in closer-to-real conditions.
The institute installed a STED (Stimulated Emission Depletion) microscope that uses doughnut-shaped lasers and multi-colour fluorescent tags to produce super-resolved images of much thicker samples than conventional optical microscopes.
Researchers will apply the instrument to study how human bowel cells form and how those processes break down in inflammatory bowel disease, using thick organoids and patient-derived tissue.
Scientists at the Rosalind Franklin Institute have installed a STED (Stimulated Emission Depletion) optical microscope intended to give a clearer view of the small-scale processes that build and maintain the human bowel. The hardware lets researchers study thicker, live tissue and organoid samples with much higher resolution than standard optical microscopes.
STED microscopy is a form of super-resolved fluorescence imaging. The system uses lasers shaped like a doughnut to restrict which fluorescent molecules emit light, boosting resolution beyond the limits of conventional light microscopy. The instrument also supports multiple fluorescent tags in one sample so researchers can label and follow different molecules or structures by colour.
What it allows researchers to do differently
Dr Karina Pombo-Garcia, group leader of the lab where the instrument is based, said the microscope lets teams "look at very, very tiny processes inside cells with a very high resolution" and that they can observe those processes live. She added it enables the team to see "how proteins come together to assemble complexes and how these go wrong in disease."
One of the first programmes to use the microscope targets the formation of cells in the developing human bowel and the changes that occur when those processes fail in conditions such as inflammatory bowel disease (IBD). IBD includes conditions like Crohn's disease and ulcerative colitis, where tissue structure and cellular behaviour in the gut go awry.
By imaging organoids and patient-derived tissue in three dimensions while following multiple molecular markers, researchers plan to connect specific molecular assemblies and cellular behaviours to the tissue-level abnormalities seen in IBD. The hope is that seeing these assemblies in their near-native context will identify precise steps where disease processes begin.
Science minister Chris McDonald officially opened the microscope and confirmed a funding package of £160 million to be shared between the Rosalind Franklin Institute and the Royce Institute in Manchester. The minister said the funding represented good value and noted that STFC (Science and Technology Facilities Council) will make independent prioritisation decisions affecting how research funds are allocated.
Teams will begin a programme of live imaging experiments on organoids and patient-derived tissues focused on bowel development and IBD. The combination of super-resolution detail and thicker sample capability will be the primary test of whether observations translate into new targets for treatment or diagnostics.
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