Dr Alice Pyne
MSci, MRes, EngD
School of Chemical, Materials and Biological Engineering
Senior Lecturer in Soft Matter & Polymers
UKRI Future Leaders Fellow
+44 114 222 5969
Full contact details
School of Chemical, Materials and Biological Engineering
Sir Robert Hadfield Building
Mappin Street
Sheffield
S1 3JD
- Profile
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I am a Senior Lecturer and UKRI Future Leaders Fellow at the University of Sheffield. Following my undergraduate degree in Physics at Bristol and my EngD in Biophysics at UCL, I was awarded EPSRC and MRC fellowships to establish my independent research group at UCL. I moved to Sheffield in 2019 as a Lecturer, where I established the Henry Royce Nanocharacterisation Laboratory
My research focusses on developing high-resolution Atomic Force Microscopy (AFM) imaging methods for structural characterisation of biomolecules in solution. I have pioneered single-molecule imaging studies of the DNA double helix, including unique time-resolved imaging at the atomic scale, showing DNA molecules twisting and “dancing” in ways that had not previously been imaged. I have a keen interest in bioimage analysis, and have developed an automated image analysis pipeline, TopoStats, that combines AFM image correction, molecule identification, and tracing into a single tool.
- Qualifications
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- EngD Biophysics, University College London & the National Physical Laboratory, High Resolution Atomic Force Microscopy of Functional Biological Molecules (2015)
- MRes (Hons) Distinction, UCL, Molecular Modelling and Materials Science (2011)
- MSci (Hons) Physics, University of Bristol (2009)
- Research interests
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My research is highly interdisciplinary, working closely with industry to engineer new high-resolution Atomic Force Microscopy (AFM) technologies which enable us to understand the fundamental properties of biological molecules at the nanoscale. These technologies have enabled us to perform unique time-resolved imaging of DNA at the sub-molecular scale. Beyond hardware, I am spearheading the development of an open-source, automated AFM image analysis pipeline, TopoStats, which is becoming the field’s “gold standard”, for which I was awarded the 2023 Royal Microscopy Society’s AFM & SPM award. Our current research impact spans fundamental biological understanding to therapeutic development.
Key research interests:
- Atomic Force Microscopy
- Open-source image analysis pipelines
- Structure and Function of nucleic acids
- Materials surface characterisation at the nanoscale
- Publications
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Journal articles
- Structural basis of negative supercoiling induced Cas9 off-targeting. Biophysical Journal, 123(3), 320a-320a.
- Direct observation of Shelterin dynamics and T-loop formation at telomeres. Biophysical Journal, 122(3), 9a-10a.
- Atomic Force Microscopy of DNA and DNA-Protein Interactions.. Methods Mol Biol, 2476, 43-62.
- Atomic force microscopy—a tool for structural and translational DNA research. APL Bioengineering, 5.
- Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides. Nature Communications, 12. View this article in WRRO
- TopoStats – A program for automated tracing of biomolecules from AFM images. Methods. View this article in WRRO
- Imaging the Effects of Peptide Materials on Phospholipid Membranes by Atomic Force Microscopy, 225-235.
- Cantilever Sensors for Rapid Optical Antimicrobial Sensitivity Testing. ACS Sensors, 5(10), 3133-3139. View this article in WRRO
- Imaging live bacteria at the nanoscale: comparison of immobilisation strategies. The Analyst, 144(23), 6944-6952. View this article in WRRO
- Single-molecule kinetics of pore assembly by the membrane attack complex. Nature Communications, 10(1), ---. View this article in WRRO
- PEGylated surfaces for the study of DNA–protein interactions by atomic force microscopy. Nanoscale, 11(42), 20072-20080. View this article in WRRO
- Bacterial killing by complement requires membrane attack complex formation via surface‐bound C5 convertases. The EMBO Journal, 38(4).
- Author Correction: Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms. Scientific Reports, 8(1).
- Tuneable poration : host defense peptides as sequence probes for antimicrobial mechanisms. Scientific Reports, 8(1). View this article in WRRO
- DNA Origami Inside-Out Viruses. ACS Synthetic Biology, 7(3), 767-773.
- The role of C5 convertases in membrane attack complex dependent killing of Gram-negative bacteria. Molecular Immunology, 89, 154-154.
- Engineering monolayer poration for rapid exfoliation of microbial membranes. Chemical Science, 8(2), 1105-1115.
- Biomimetic Hybrid Nanocontainers with Selective Permeability. Angewandte Chemie, 128(37), 11272-11275.
- Biomimetic Hybrid Nanocontainers with Selective Permeability. Angewandte Chemie International Edition, 55(37), 11106-11109.
- Single-Molecule Reconstruction of Oligonucleotide Secondary Structure by Atomic Force Microscopy. Small, 10(16), 3257-3261. View this article in WRRO
- Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers. Proceedings of the National Academy of Sciences, 110(22), 8918-8923.
- Atomic Force Microscopy with Nanoscale Cantilevers Resolves Different Structural Conformations of the DNA Double Helix. Nano Letters, 12(7), 3846-3850.
- High-speed atomic force microscopy of dental enamel dissolution in citric acid. Archives of Histology and Cytology, 72(4/5), 209-215.
- Complement-mediated killing of Escherichia coli by mechanical destabilization of the cell envelope. The EMBO Journal.
- Multiscale topological analysis of kinetoplast DNA via high resolution AFM. Physical Chemistry Chemical Physics.
- Lipidated DNA Nanostructures Target and Rupture Bacterial Membranes. Small.
- Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription. Nature Communications, 14(1).
- Studies of G-quadruplexes formed within self-assembled DNA mini-circles. Chemical Communications, 52(84), 12454-12457.
Chapters
- Online Content: Physical and Structural Techniques Applied to Nucleic Acids, Nucleic Acids in Chemistry and Biology (pp. E1-E50). The Royal Society of Chemistry
- Imaging DNA Structure by Atomic Force Microscopy, Methods in Molecular Biology (pp. 47-60). Springer New York
- Nucleic Acids in Chemistry and Biology In Blackburn GM, Gait MJ, Loakes D & Williams DM (Ed.) The Royal Society of Chemistry
Conference proceedings papers
- Probing antimicrobial mechanisms for effective strategies to overcome resistance. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, Vol. 48 (pp S223-S223)
- Visualisation of DNA conformational changes in situ at nanometre resolution. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, Vol. 46 (pp S369-S369)
- A combinatorial single-molecule study of ligand-gated ion channels and monoclonal antibodies. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, Vol. 46 (pp S371-S371)
- Investigating the mechanism of action of a novel antimicrobial peptide on live E. coli cells. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, Vol. 46 (pp S389-S389)
Software / Code
Datasets
- 2 Methods for DNA Adsorption on a Mica Substrate for AFM Imaging in Fluid v1 (protocols.io.bncjmaun).
- Atomic Force Microscopy of DNA and DNA-Protein Interactions v1 (protocols.io.bncemate).
- 3 Pre-imaging Setup for High Resolution AFM in Fluid v1 (protocols.io.bncnmave).
- 5 Methods for DNA-protein imaging by AFM in fluid v1 (protocols.io.bncqmavw).
- 1 Preparation of Mica Substrate v1 (protocols.io.bnb2maqe).
- 4 Optimizing AFM Imaging in PFT for High Resolution AFM Imaging on DNA v1 (protocols.io.bncpmavn).
Other
Preprints
- Multiscale topological analysis of kinetoplast DNA via high-resolution AFM, Cold Spring Harbor Laboratory.
- Under or Over? Tracing Complex DNA Topologies with High Resolution Atomic Force Microscopy, Cold Spring Harbor Laboratory.
- Complement-mediated killing of bacteria by mechanical destabilization of the cell envelope, Cold Spring Harbor Laboratory.
- Single-molecule kinetics of pore assembly by the membrane attack complex, bioRxiv.
- Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription, Cold Spring Harbor Laboratory.
- TopoStats – a program for automated tracing of biomolecules from AFM images.
- Base-pair resolution analysis of the effect of supercoiling on DNA flexibility and major groove recognition by triplex-forming oligonucleotides.
- Imaging live bacteria at the nanoscale: comparison of immobilisation strategies.
- PEGylated surfaces for the study of DNA-protein interactions by atomic force microscopy.
- Cantilever Sensors for Rapid Optical Antimicrobial Sensitivity Testing.
- Research group
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PhD Students:
- Daniel Rollins (AFM analysis of supercoiled DNA interactions)
- Mingxue Du (TopoStats: Automating AFM analysis of DNA & protein interactions)
- Libby Holmes (Complex DNA structures in cancer)
- Max Gamil (Deep probabilistic models for analysing complex DNA structures)
PhD Students (UCL):
Kavit Main (Single molecule insights into DNA-Topoiomerase interactions)
- Professional activities and memberships
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- Fellow of the Royal Microscopy Society
- Committee member of the British Biophysical Society
- Committee member of the Royal Microscopy Society - vice chair of the Data Analysis in Microscopy (DAIM) subgroup