Super-resolution microscopy operating at approximately 20-nanometre resolution—roughly ten times beyond conventional light microscopy—is being deployed by scientists at the Rosalind Franklin Institute to investigate the cellular mechanisms of inflammatory bowel disease (IBD), according to researchers at the institute. Housed at the Harwell Science and Innovation Campus in Oxfordshire, the specialized Stimulated Emission Depletion (STED) microscope allows researchers to examine how individual proteins organize at junctions between intestinal cells to maintain the gut barrier.
How STED Microscopy Operates at the Nanoscale
The STED microscope utilizes a second, doughnut-shaped depletion laser alongside a primary laser beam. According to the Rosalind Franklin Institute, the outer ring of the depletion laser actively quenches fluorescence emitted by the first beam while leaving the center unaffected. This allows researchers to detect fluorescent light from the exact focal point in extreme detail.
Furthermore, the system features multiplexing capabilities. This function permits the visualization of multiple biomolecules—including proteins, lipids, and glycans—each labeled with distinct fluorescent tags in a single sample. According to project details, the equipment includes distortion-correcting mirrors and a temperature-controlled stage capable of maintaining conditions close to normal body temperature for living cells and mini-organs.
Did you know? The STED microscope at the Rosalind Franklin Institute is currently one of a kind in the UK, combining live-cell imaging with nanoscopic resolution to study human tissue samples.
Investigating Gut Barrier Failure in Crohn’s Disease and Ulcerative Colitis
More than half a million people in the UK live with IBD, primarily Crohn’s disease and ulcerative colitis, according to data cited by the British Society of Gastroenterology. Dr. Karina Pombo-Garcia, who leads the research team at the Rosalind Franklin Institute, noted that conventional microscopy shows when the gut barrier is disrupted, but STED microscopy reveals precisely how and where the disruption happens.
“At this scale, we can resolve how individual proteins organise at the junctions between intestinal cells to build and maintain the barrier that protects us from the contents of the gut,” Dr. Pombo-Garcia told EMJ. She explained that by examining thicker human samples, including patient-derived intestinal organoids, researchers can compare healthy and IBD-derived samples to identify the earliest molecular changes causing barrier failure.
Funding and Medical Innovation Backing in the UK
According to a report published by the British Society of Gastroenterology, 24% of adults living with IBD find it hard to cope with the condition, and one in seven cases are diagnosed through an emergency hospital admission. Science Minister Chris McDonald unveiled the STED microscope alongside a five-year £67.7 million investment from the Engineering and Physical Sciences Research Council directed to the Rosalind Franklin Institute.
In addition, the Henry Royce Institute is set to receive £90 million over the same five-year period for materials research. These allocations were outlined in the core budget of UK Research and Innovation (UKRI) as part of the 2025 spending review. Dr. Pombo-Garcia stated that the new funding provides an opportunity to connect protein-level observations directly with patient outcomes, helping to identify potential therapeutic targets that can restore normal nanoscale organization in the gut barrier.
Frequently Asked Questions
What is STED microscopy?
Stimulated Emission Depletion (STED) microscopy is an advanced imaging technique that uses a secondary depletion laser to bypass the diffraction limit of standard light microscopes, achieving roughly ten times higher resolution.
How does IBD affect the gut barrier?
In inflammatory bowel disease, the intestinal barrier becomes damaged and permeable, allowing chronic inflammation to persist. Researchers are using high-resolution imaging to study the exact molecular changes causing this breakdown.
How many people live with IBD in the UK?
More than half a million people in the UK live with inflammatory bowel disease, with Crohn’s disease and ulcerative colitis representing the two primary forms, according to British Society of Gastroenterology figures.
What funding has been allocated for this research?
The Rosalind Franklin Institute received a share of a five-year £67.7 million investment from the Engineering and Physical Sciences Research Council, announced by Science Minister Chris McDonald.
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