University of
We develop and apply single-molecule fluorescence and force spectroscopy to understand how proteins, DNA and RNA fold, interact and regulate life — without the averaging that hides what individual molecules actually do.
The HeraldDeadline News
We use and develop novel physical techniques to study biomolecular interactions — proteins, DNA and RNA — at the level of single molecules. Our toolkit combines single-molecule FRET, optical and magnetic tweezers and super-resolution imaging with in-house instrumentation and new fluorescent chemistries.
Single-molecule techniques let us measure intermediates and follow time-dependent pathways of reactions and folding mechanisms that are difficult or impossible to synchronise at the ensemble level. Because spatial and temporal averaging is avoided, phenomena that remain hidden in bulk measurements can be discovered directly.
Our lab sits across the School of Physics & Astronomy and the Biomedical Science Research Complex (School of Biology). Students with physics and chemistry backgrounds apply their expertise in instrumentation, synthesis and analysis to biological problems, while students from biology gain hands-on access to state-of-the-art physical technologies that expand their research capabilities.
The lab is led by Prof. Carlos Penedo and is a member of the Centre of Biophotonics, which brings together the Schools of Medicine, Physics, Neuroscience and Biology at St Andrews, and of the Biomedical Science Research Complex, integrating researchers across Physics, Chemistry, Biology and Medicine. Established in 2006, the lab brings together users and developers of single-molecule methods to investigate fundamental molecular and cellular mechanisms involved in health and disease.
Our work applies elements of chemistry and physics to the complexity of biological systems. Some projects build the tools — dyes, labelling chemistries, instruments — and others use them to watch molecular machines in action.
Metabolite-sensing RNAs that switch bacterial genes on and off. We watch them fold as they emerge from RNA polymerase, in native transcription complexes, at single-nucleotide resolution.
CollaboratorsDaniel Lafontaine (Université de Sherbrooke, Canada)
Read moreHelicases, nucleases, single-stranded binding proteins and CRISPR effectors: how they load, unwind and process nucleic acids, and how G-quadruplex structures are remodelled during repair.
CollaboratorsMalcolm F. White (St Andrews), Helder Ferreira (St Andrews), Katrin Paeschke (Bonn), Sylvia Fanucchi (University of the Witwatersrand, Johannesburg, South Africa)
Read moreInsulin is stored as zinc-stabilised hexamers that must fall apart to act. With FRET-labelled insulin, single-molecule TIRF and zero-mode waveguides we follow hexamer assembly and disassembly in real time, and how albumin, fatty acids and Zn²⁺ tune it — from the test tube to pancreatic β-cells.
CollaboratorsAlan Stewart (St Andrews), James Cantley (Dundee)
Read moreOptical and magnetic tweezers combined with fluorescence to apply and measure piconewton forces on single proteins, DNA and RNA conformations and their complexes with multisubunit complexes.
Read moreBrighter, more photostable fluorophores, orthogonal labelling chemistries and TWIN-FRET equilibrium-encoded pairs that remove the labelling barrier for smFRET.
Read moreSingle-molecule spectroscopy of light-emitting organic semiconductors in solution, resolving conformational switching and β-phase content chain by chain.
CollaboratorsIfor Samuel (St Andrews)
Read moreSequence-independent imaging and manipulation of nucleic acids, sub-diffraction imaging of RNA in cells, single-particle tracking of viral fusion, and correlative force–fluorescence measurements from molecules to whole cells.
CollaboratorsJuan Varela (St Andrews), John Danial (St Andrews)
Read moreThe single-molecule toolkit available in the lab, most of it built or adapted in-house.
Objective- and prism-type TIRF, confocal smFRET (ALEX / PIE), fluorescence lifetime, single-molecule photobleaching and super-resolution (STORM/PALM).
LUMICKS C-Trap correlative optical tweezers–confocal, magnetic tweezers and force–FRET hybrids.
In-house MATLAB/Python pipelines for trace extraction, hidden-Markov modelling and kinetic analysis (TRACER).
Physicists, chemists and biologists working side by side. We are always keen to hear from students and postdocs who want to bring a new technique to a biological question — or a new question to a technique.
Carlos is an experimental biophysicist who develops optical instrumentation for single-molecule microscopy and spectroscopy and applies it to the structural dynamics of biomolecules and of polymer materials used in opto-electronics. He holds a joint appointment as Professor in the School of Physics & Astronomy and the School of Biology, and was co-founder and Director of the Centre of Biophotonics between 2019 and 2026. Before St Andrews he was a postdoctoral fellow at Trinity College Dublin and the University of Dundee and a development engineer at Edinburgh Instruments (now part of Techcomp); he joined St Andrews in 2006 as a SUPA Advanced Fellow, becoming Lecturer in 2011, Reader in 2018 and Professor in 2022.
Single-molecule spectroscopy and super-resolution imaging of conjugated polymers.
Remodelling of G-quadruplex structures by the nucleotide excision repair machinery.
Janus-face fluorinated molecules as DNA probes; single-molecule imaging.
Single-molecule approaches to zinc-dependent insulin and albumin interactions.
Single-molecule studies of enzyme mechanisms.
Optical and magnetic tweezers; single-molecule imaging of GPCRs.
CRISPR effector complexes studied with single-molecule techniques.
Peer-reviewed work from the lab and its collaborators. The complete record is on Google Scholar.
Our research is supported by UK research councils, charities and the University of St Andrews. We are grateful to all of them, and to the collaborators who make joint applications possible.
Lead: Alan Stewart (St Andrews); Co-leads: Carlos Penedo, James Cantley (Dundee). £1.05M.
PI: David O'Hagan; Co-PIs: Carlos Penedo, Georg Hähner. £752k.
Lead PI: Carlos Penedo. £642k.
PIs: Carlos Penedo (St Andrews) and Katrin Paeschke (Bonn).
PIs: David O'Hagan and Carlos Penedo.
Lead PI: Alison Roberts (James Hutton Institute); Co-PI: Carlos Penedo. £810k.
Lead PI: Carlos Penedo; Co-PIs: Juan Varela, Terry Smith.
Lead PI: Janet Lovett; Co-PI: Carlos Penedo. £353k.
Lead PI: Carlos Penedo; Co-PIs: Ifor Samuel, Peter Skabara (Glasgow). £1.1M.
PIs: Carlos Penedo and Sylvia Fanucchi. £102k.
PI: Malcolm F. White; Co-PI: Carlos Penedo. £604k.
PI: Edward Anderson (Oxford); Co-PIs: Janet Lovett, Carlos Penedo. £187k.
PI: Bela Bode; Co-PI: Carlos Penedo. £200k.
Fellow: Sankar Jana; PI: Carlos Penedo. £96k.
PI: Carlos Penedo; Co-PI: Ifor Samuel; with Peter Skabara (Strathclyde). £500k.
PI: Malcolm F. White; Co-PIs: Jim Naismith, Carlos Penedo. £950k.
PI: Carlos Penedo; Co-PI: Malcolm F. White. £415k.
Modules contributed across the Schools of Physics & Astronomy and Biology.
PH5016Biophotonics (module coordinator)PH4105Physics Lab 2PH3014Transferable and Professional SkillsBL4225Seeing is BelievingBL4201Experimental Honours ProjectPH4043Studies in Physics and Chemistry – Transferable Skills (module coordinator)PH1012Physics 1B – Group Discovery ProjectPH3014Transferable and Professional SkillsBL2306BiochemistryBL3301Protein Structure and FunctionBL4201Experimental Honours ProjectAn annual hands-on school run by the Centre of Biophotonics each June, bringing more than 30 internal and international participants into the labs to use advanced microscopy and spectroscopy on real samples.
Undergraduate, MSc and PhD students join the lab for research projects spanning optics, instrument building, biophysics and data analysis. Get in touch if you are interested in a project.
Much of our analysis relies on software written in the lab. We make it available to the single-molecule community — for access, contact Carlos Penedo at jcp10@st-andrews.ac.uk.
MATLAB · smFRETA graphical environment for single-molecule FRET analysis: extraction of donor and acceptor traces from movies, correction and selection of molecules, FRET histograms, dwell-time analysis and hidden-Markov modelling via an integrated ebFRET module, with export to common formats. Comes with a detailed user guide.
In-house scripts for trace extraction, kinetic analysis, force–fluorescence correlation and batch processing of single-molecule data sets, developed alongside our experiments.
We welcome enquiries from prospective PhD students, postdocs and visiting researchers with backgrounds in physics, chemistry, biology or engineering. Write to Carlos with a CV and a few lines about what you would like to work on.
A three-year, full-time Research Fellow post on our BBSRC-funded insulin project, led by Dr Alan Stewart (Project lead, School of Medicine) and Prof. Carlos Penedo (Project co-lead), investigating how zinc, pH, serum albumin and free fatty acids regulate insulin storage and release in pancreatic beta-cells. The postholder will use advanced fluorescence and imaging approaches, including FRET-based assays and fluorescence lifetime imaging (FLIM).
We are looking for a PhD (or near completion) in cell biology, biochemistry, biophysics, molecular biology or a related discipline, with expertise in advanced fluorescence microscopy, live-cell imaging, protein biophysics or quantitative biological sciences. £38,784–£42,254 per annum; start January 2027. Ref. AR3324.
We are happy to host and co-write applications for Marie Skłodowska-Curie, Royal Society Newton, Leverhulme, EMBO and similar fellowships. Get in touch well ahead of deadlines so we can shape a project together.
Undergraduate summer projects and MSc placements are also available through the Centre of Biophotonics summer school.
Papers, grants, arrivals and equipment.
Congratulations to Amirmohammad Khodabandeh, who received the Best Poster Award at the Ludwig conference on Alternative Nucleic Acid Conformations in Health and Disease (A to Z 2026) at Worcester College, Oxford.
Olga Filippova attends the 31st International Workshop on Single Molecule Spectroscopy and Super-resolution Microscopy, organised by PicoQuant in Berlin, 6–8 October 2026, where she presents her work on the single-molecule photophysics of conjugated polymers.
A Refeyn TwoMP mass photometer is arriving at the Biomedical Science Research Complex. Mass photometry weighs individual biomolecules from the light they scatter, giving mass distributions of complexes in solution within minutes and without labels — a valuable addition to the portfolio of single-molecule methods available in the lab.
Amirmohammad Khodabandeh attends the Ludwig Conference on Alternative Nucleic Acid Conformations in Health and Disease at Worcester College, Oxford, 28 September – 2 October 2026.
Yu represents the lab at the Biophysical Society thematic meeting marking 30 years of single-molecule FRET, Tutzing, Germany, 21–25 September 2026.
Carlos co-organises the School of Physics & Astronomy industry day on imaging, sensing and spectroscopy for health, with talks from Fujifilm, Optos, Singular Photonics and the RS Macdonald Trust, among others.
Our BBSRC award with Alan Stewart and James Cantley was covered by The Herald, Deadline News and Diabetes UK, among others.
Invited talk at the joint meeting of the British and German Biophysical Societies, Glasgow, 15–16 July 2026.
Preprint on ChemRxiv: a zinc–albumin–fatty-acid axis regulates how insulin hexamers fall apart (doi:10.26434/chemrxiv.15006839/v1).
Together with Dr Alan Stewart (School of Medicine, St Andrews) and Prof James Cantley (University of Dundee), we have been awarded a three-year, £1.05M BBSRC grant, "Zinc-dependent insulin multimerisation in pancreatic beta-cells and its implications for glycaemic control". The St Andrews arm will use single-molecule TIRF, zero-mode waveguides and FRET to follow how insulin hexamers assemble and fall apart, and will fund a postdoctoral position jointly supervised by Carlos and Alan. A related preprint describing our FRET-based insulin disassembly assay is on ChemRxiv. The award was covered by The Herald ("St Andrews and Dundee researchers to advance insulin research", 28 July 2026).
With Katrin Paeschke (Bonn) and Harald Schwalbe (Frankfurt), we show in Nucleic Acids Research that the Zuo1 C-terminal domain binds and stabilises DNA G4 structures in S. cerevisiae (doi:10.1093/nar/gkaf1055).
Room 1.08, BSRC Annex
Biomedical Science Research Complex
North Haugh, St Andrews KY16 9SS
Scotland, UK
+44 (0)1334 463106
jcp10@st-andrews.ac.uk
