Research Areas - (22) Single-Molecule FRET

Full path: Biology > Biophysics > Quantum Biology / Biosensing > Single-Molecule FRET

Department(s)/lab(s): Physics & Astronomy โ€“ AMOPP | Bain Lab (Femtosecond Laser Spectroscopy and Super-Resolution Biosensing) @ UCL
Summary:

Bain develops advanced laser spectroscopy and super-resolution microscopy techniques for biological applications. Research directions: (1) Femtosecond time-resolved STED (stimulated emission depletion) โ€” combining sub-diffraction spatial resolution with picosecond time resolution to study FRET dynamics in live cells with both spatial and lifetime precision; (2) Time-resolved polarized fluorescence โ€” probing orientation distributions and rotational dynamics of fluorophores; (3) CW STED fluorescence lifetime reconstruction โ€” lower-photodose STED for longer live-cell imaging; (4) Single-molecule FRET to study protein-protein interactions; (5) Single-particle tracking of membrane receptors relevant to viral entry and cancer signaling. Former PhD students include Siรขn Culley (now King's College, SMLM).

Department(s)/lab(s): Physics & Astronomy โ€“ Biophysics | Bell Lab (DNA Nanotechnology and Optical Biosensing) @ UCL
Summary:

Bell's group uses DNA nanotechnology and advanced optical microscopy for single-molecule biosensing. Research directions: (1) DNA-based biosensing โ€” DNA origami structures as programmable biosensing platforms; using structural switching of DNA nanodevices to sense specific biomolecules with single-molecule sensitivity; (2) Super-resolution microscopy with DNA โ€” DNA-PAINT and FRET-based single-molecule localization for mapping molecular architectures in cells; (3) Solid-state nanopores โ€” DNA-threaded through nanopores as a precision biosensor for protein identification and force measurement; (4) Multiplexed single-molecule detection โ€” combining DNA-based sensors with optical readout for parallel biomolecule profiling. New group established at UCL, strong biosensing focus.

Department(s)/lab(s): EMBL Australia Node in Single Molecule Science, UNSW Medicine and Health | Molecular Machines Group (Boecking) @ UNSW
Summary:

Boecking leads the Molecular Machines Group and is acting director of the EMBL Australia Node in Single Molecule Science. The group reconstitutes molecular machines โ€” clathrin coat disassembly, HIV capsid assembly and uncoating, pore-forming toxins โ€” and watches them work one molecule at a time by TIRF, interferometric scattering (mass photometry) and fluorescence fluctuation methods, resolving short-lived intermediates that ensemble kinetics averages into invisibility. He trained originally in surface chemistry and biosensors with Gooding, which gives the group unusual competence in engineering the surfaces these assays run on. Positioned against the established body of NV-ensemble quantum sensing work โ€” DEER, nanoscale NMR and T1 relaxometry protocols operating at pT/sqrt(Hz) field sensitivity โ€” the argument for single-molecule methods over ensemble ones is identical to the argument for pushing NV sensing below its pT/sqrt(Hz) ensemble regime: the interesting biology lives in heterogeneity and in transient states that averaging destroys. Strong methodological neighbour for a quantum-biosensing candidate.

Department(s)/lab(s): Physics | Chu Lab @ Stanford
Summary:

Nobel laureate Steven Chu's group spans laser cooling/trapping of atoms and single-molecule biophysics, using optical and magnetic tweezers and single-molecule fluorescence to study DNA/RNA folding, molecular motors, and signal transduction -- one of the earliest applications of AMO-derived single-particle measurement precision to living systems.

Department(s)/lab(s): School of Physics | Curmi Molecular Biophysics Laboratory @ UNSW
Summary:

Curmi is a structural and single-molecule biophysicist whose most-cited work is on the light-harvesting antenna proteins of cryptophyte algae, where he and collaborators reported long-lived electronic coherence at ambient temperature โ€” one of the founding results of the quantum-biology field and still one of its most argued-over. His group determines the structures of these antenna complexes and engineers them, and separately works on protein-based molecular motors and on single-molecule fluorescence and FRET measurements of conformational dynamics. Positioned against the established body of NV-ensemble quantum sensing work โ€” DEER, nanoscale NMR and T1 relaxometry protocols operating at pT/sqrt(Hz) field sensitivity โ€” Curmi supplies the biological systems in which quantum coherence is actually claimed to matter; a pT/sqrt(Hz)-class spin sensor capable of watching radical-pair or exciton dynamics in situ would be aimed at exactly the questions his structures raise. Preferred attribute present: genuine quantum-biology substrate rather than a quantum-flavoured metaphor.

Department(s)/lab(s): EMBL Australia Node in Single Molecule Science, UNSW Medicine and Health | Gambin Single Molecule Biophysics Group @ UNSW
Summary:

Gambin was the first EMBL Australia group leader appointed to Single Molecule Science. His signature method combines cell-free protein expression with two-colour single-molecule coincidence and fluctuation spectroscopy, which sidesteps purification entirely: proteins are expressed, labelled and measured in lysate, an order of magnitude faster than conventional interaction assays. The biology is protein self-association and aggregation โ€” alpha-synuclein in Parkinson's, cardiac and muscular disease proteins โ€” where the size distribution of oligomers, not the mean, is the quantity of interest. Positioned against the established body of NV-ensemble quantum sensing work โ€” DEER, nanoscale NMR and T1 relaxometry protocols operating at pT/sqrt(Hz) field sensitivity โ€” the conceptual overlap with quantum biosensing is the insistence on distributions over averages, and his aggregation systems (paramagnetic-species-generating, redox-active amyloid) are a plausible target for T1-relaxometry-based NV detection at pT/sqrt(Hz) in the near term.

Department(s)/lab(s): Imaging Physics (ImPhys) | Geertsema Lab @ TU Delft
Summary:

Hylkje Geertsema uses single-molecule super-resolution fluorescence microscopy (TIRF, SMLM, PALM/STORM) to study DNA replication dynamics. Her lab visualises and quantifies individual replication proteins at replication forks in living cells to understand the kinetics and fidelity of DNA copying. Research focuses on measuring spatiotemporal dynamics of protein assemblies during DNA metabolism with nanometre resolution.

Department(s)/lab(s): Physics & Astronomy โ€“ Photon Science Institute | Graham Group (SERS and Nanoplasmonic Biosensing) @ Manchester
Summary:

Graham's group develops SERS-based nanoplasmonic sensing platforms for biomedical applications. Research directions: (1) SERS nanogap substrates โ€” engineering colloidal gold and silver nanostructure clusters with reproducible, high-enhancement nanogaps for single-molecule SERS detection; (2) In vivo SERS โ€” intravenous SERS nanotags for tumor imaging and multiplexed biomarker detection in living organisms; (3) Microfluidic SERS โ€” integrating SERS probes in microfluidic channels for continuous monitoring of circulating biomarkers; (4) Quantitative SERS โ€” calibration strategies for absolute analyte quantification for clinical diagnostics. Extreme sensitivity (single-molecule) relevant to quantum-enhanced optical sensing.

Department(s)/lab(s): Physics & Astronomy โ€“ Biophysics & London Centre for Nanotechnology | Hoogenboom Lab (High-Speed AFM and Nanoscale Biophysics) @ UCL
Summary:

Hoogenboom leads a biophysics group at UCL specializing in high-speed atomic force microscopy. Research directions: (1) High-speed AFM โ€” imaging conformational dynamics of DNA, proteins (including membrane channels), and chromatin at ms time resolution and sub-nm spatial resolution in aqueous conditions; (2) Nuclear pore complex โ€” mapping transport selectivity and structure of NPCs in native nuclear envelopes using AFM; (3) Antimicrobial mechanisms โ€” imaging membrane disruption by antimicrobial peptides in real time; (4) AFM-based force spectroscopy โ€” measuring single-molecule interaction forces in chromatin and protein assemblies. Strong relevance to biological sensing at the single-molecule level.

Department(s)/lab(s): Physics & Astronomy โ€“ Biophysics | Jones Lab (Optical Tweezers Biophysics) @ UCL
Summary:

Jones's group develops optical tweezers instrumentation for biological applications. Research directions: (1) Single-cell mechanics โ€” using optical traps to apply calibrated forces to cells and measure viscoelastic properties relevant to cancer invasion and immune response; (2) Motor protein biophysics โ€” measuring force-velocity curves of kinesin/myosin motors at the single-molecule level; (3) Optical sorting โ€” holographic optical tweezers for cell sorting by mechanical phenotype; (4) Instrument development โ€” fast-switching AOD-based traps, quantitative phase imaging combined with force measurement. Sensitive to pN forces, combining biosensing with fundamental biophysics.