Research Areas - (3) Single-Molecule Imaging of Protein Misfolding and Neurodegeneration

Full path: Biology > Biophysics > Quantum Biology / Biosensing > Super-resolution Microscopy > Single-Molecule Imaging of Protein Misfolding and Neurodegeneration

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 — clathrin coat disassembly, HIV capsid assembly and uncoating, pore-forming toxins — 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 — DEER, nanoscale NMR and T1 relaxometry protocols operating at pT/sqrt(Hz) field sensitivity — 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): 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 — alpha-synuclein in Parkinson's, cardiac and muscular disease proteins — 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 — DEER, nanoscale NMR and T1 relaxometry protocols operating at pT/sqrt(Hz) field sensitivity — 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): Chemistry (Yusuf Hamied Department of Chemistry) | Klenerman Group @ Cambridge
Summary:

Klenerman develops and applies single-molecule fluorescence and scanning-probe methods (including nanopipette scanning ion-conductance microscopy and a single-objective oblique-plane light-sheet microscope) to study protein misfolding and aggregation in neurodegenerative disease, alongside his earlier work co-inventing next-generation DNA sequencing.