Not everything we study starts in the brain. The same tools we use to count and characterise individual protein aggregates, to resolve protein complexes far below the diffraction limit, and to profile the vesicles that cells release into the blood are increasingly applied to a much wider range of human disease.
Why single molecule methods?
Bulk measurements report an average over millions of molecules. That average hides the biology that matters: rare misfolded or aggregated species, a small subpopulation of cells that behaves differently, or a biomarker present at vanishingly low concentration early in disease. Single molecule methods count and characterise individual molecules, so heterogeneity becomes the measurement rather than a nuisance to be averaged away. What so often separates healthy from diseased tissue is exactly this variation between individual molecules and cells.
Super resolution microscopy does the same in space, resolving protein complexes at the nanoscale inside intact cells and tissue, beyond the roughly 200 nm limit of conventional light microscopy.
Together these approaches let us detect disease earlier, at lower concentration, and with a mechanistic read out rather than a bulk signal.
Diseases we work on
Vascular calcification, with Dr Vicky MacRae (Roslin Institute). Arterial calcification stiffens blood vessels and drives cardiovascular disease. We use super resolution imaging and machine learning to ask how mitochondrial function and mitochondrial morphology in vascular smooth muscle cells underpin calcification, and what happens when specific fission and fusion regulators are knocked out or overexpressed.
Ovarian cancer, with Dr Mike Rimmer (University of Edinburgh). Ovarian cancer is often detected late, when treatment options are limited. We are developing a single molecule blood test for its earlier detection, extending the group's VISTA platform to profile tumour associated antigens displayed on extracellular vesicles.
Extracellular vesicles, with Prof Amy Buck (University of Edinburgh). Cells shed extracellular vesicles carrying proteins and RNA from their parent cell, making them a rich and accessible source of biomarkers, and a demanding analytical problem, because they are small, heterogeneous and present in complex biofluids. We characterise individual vesicles and their cargo using single molecule confocal microscopy and nanopore sensing.
Team members
- Tiasa Das
- Xiao Tan
- Sofia Olendraru
- Dan Edwards
- Krzysztof Bąk
Collaborators
- Dr Vicky MacRae, vascular calcification (Roslin Institute)
- Dr Mike Rimmer, ovarian cancer
- Prof Amy Buck, extracellular vesicles
Selected Recent Publications
Live high-content imaging with automated analysis reveals mitochondrial changes during vascular calcification.
Preprint, bioRxiv (2026). https://doi.org/10.64898/2026.02.03.703459
Fluorescence characterization of extracellular vesicles using single-molecule confocal microscopy.
Small Methods, e00907 (2025). https://doi.org/10.1002/smtd.202500907
Single-molecule validation and optimized protocols for the use of secondary nanobodies in multiplexed immunoassays.
Journal of Microscopy, 1-15 (2026). https://doi.org/10.1101/2025.02.28.640765