School of Physics, Engineering and Technology
- School of Physics, Engineering and Technology
- Research and innovation
- Physics of Life
- Single Molecule Diagnostics
Single Molecule Diagnostics:
Detecting the Molecular Nanoworld of Life and Disease using Optics, Spectroscopy, Biophotonics and Single-Molecule Microscopy
- We are a team of highly interdisciplinary researchers working at the life-sciences interface to detect and investigate the molecular nanoworld of human life and disease.
- We use major developments in microscopy and biochemical techniques to answer open questions related to human disease, with a particular focus on dementia.
- We detect, understand and exploit nanoscale structural changes in proteins, DNA and membrane systems to access new information about their function.
- Our goal is to provide a suite of transformative tools from which to more effectively detect biomarkers of disease.
The Single Molecule Diagnostics group is headed by Dr. Steve Quinn. The team works at the cutting edge of biophysics research to detect and investigate the molecular nanoworld of human life and disease.
Dr Quinn completed his PhD at the University of St Andrews, and held research positions at the University of Glasgow and the Massachusetts Institute of Technology (MIT).
The group is affiliated with the Biological Physical Sciences Interdisciplinary Network and the York Biomedical Research Institute.
Our lives have some meaning on a scale of meters, but it’s often impossible to think about ordinary, everyday existence on a scale 1000 times smaller than a fly’s eye - the so-called 'nanosale'. Yet the nanoscale is where proteins, lipids and DNA molecules - the building blocks of human life - rule the roost. By zooming into the nanoscale, our goal is to understand how many of the puzzling pathways in human disease work at the smallest possible length scale.
Our group combines cutting-edge tools from optics, spectroscopy, biology, chemistry and microscopy to detect and probe nanoscale interactions. We use state-of-the-art techniques including single-molecule imaging, biophotonics, fluorescence microscopy and ultrafast spectroscopy to explore the structure and function of biomolecules, with a particular focus on those implicated in Alzheimer’s disease
His early work led to the development of new approaches for monitoring self-assembly of the b-amyloid protein, and for the screening of novel oligomerization inhibitors. He has also investigated the effect of molecular crowding agents on biomolecular structure, developed tools and techniques for exploring carbohydrate interactions and created a series of sensing platforms for detecting toxic agents in solution. Recent work has focussed on the development of fluorescently tagged model membrane vesicles and membrane nanodiscs for exploring protein-lipid interactions and membrane disruption mechanisms.
Alzheimer's Disease
Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of toxic protein fragments in the brain. We aim to understand how these fragments grow and develop, how they manipulate and rupture cellular membranes and how to stop them. Recently, we developed new diagnostic approaches to detect and quantify blood-based protein biomarkers at clinically-relevant levels.
One analogy to the theory behind the search for an effective drug is a flooded apartment caused by a burst pipe. Drug discovery has focused on duct taping the pipe, but without understanding and preventing the root cause.
We combine major developments in biochemistry and single-molecule imaging to provide spectroscopic optical fingerprints of Alzheimer's disease on the nanoscale, providing a new suite of tools from which to more effectively and efficiently detect biomarkers and screen the next generation of therapeutics.
Key Publications:
P. A. Dalgarno, J. Juan-Colas, G. J. Hedley, L. Pineiro, M. Novo, D. C. Perez Gonzalez, I. D. W. Samuel, M. C. Leake, W. Al-Soufi, S. Johnson, J. C. Penedo & S. D. Quinn† . Unveiling the multi-step solubilization mechanism of sub-micron size vesicles by detergents. Sci. Rep. 9, 12897 (2019).
S.D. Quinn, S. Srinivasen, J. Gordon, W. He, K. L. Carraway, III, M. A. Coleman & G. S. Schlau-Cohen. Single-molecule fluorescence detection of the epidermal growth factor receptor in membrane discs. Biochemistry. 58, 286-294 (2018).
S.D. Quinn & S. W. Magennis. Optical detection of gadolinium (III) ions via quantum dot aggregation. RSC Advances. 7, 24730-24735 (2017).
S.D. Quinn, A. Rafferty, E. Dick, M. J. Morten, F. J. Kettles, C. Knox, M. Murrie & S. W. Magennis. Surface charge control of quantum dot blinking. J. Phys. Chem. C. 120, 19487-19491 (2016)
C. E. Dalton*, S. D. Quinn*, A. Rafferty, M. J. Morten, J. M. Gardiner & S. W. Magennis. Single-molecule fluorescence detection of a synthetic heparan sulfate disaccharide. ChemPhysChem. 17, 3442-3446 (2016).
L. Aitken, S. D. Quinn, D. C. Perez-Gonzalez, I. D. W. Samuel, J. C. Penedo and F. J. Gunn-Moore. Morphology-specific inhibition of b-amyloid aggregates by 17b-hydroxysteroid dehydrogenase type 10. ChemBioChem, 17, 1029-1037 (2016).
L. E. Baltierra-Jasso, M. J. Morten, L. Laflör, S. D. Quinn & S. W. Magennis. Crowding-induced hybridization of single DNA hairpins. J. Am. Chem. Soc. 137, 16020-16023 (2015).
R. T. Cameron, S. D. Quinn, L. S. Cairns, R. MacLeod, I. D. W. Samuel, B. O. Smith, J. C. Penedo & G. S. Baillie. The phosphorylation of Hsp20 enhances its association with amyloid-b to increase protection against neuronal cell death. Mol. Cell. Neurosci. 61, 46-55 (2014).
S.D. Quinn, P. A. Dalgarno, R. T. Cameron, G. J. Hedley, C. Hacker, J. M. Lucocq, G. S. Baillie, I. D. W. Samuel & J. C. Penedo. Real-time probing of b-amyloid self-assembly and inhibition using fluorescence self-quenching between neighbouring dyes. Mol. Biosyst. 10, 34-44 (2014).