Physical Chemistry Seminar: Professor Philipp Kukura, University of Oxford (Host: Todd Martinez)
"Weighing single molecules with light"
About the Seminar
The cellular processes underpinning life are orchestrated by proteins and the interactions they make with themselves and other biomolecules. A range of techniques has been developed to characterise these associations, but structural and dynamic heterogeneity remain a fundamental challenge. I will show that mass photometry based on interferometric scattering microscopy can mass-image single biomolecules in solution with nanometre precision and mass accuracy comparable to native mass spectrometry in the gas phase. Thereby, we can resolve oligomeric distributions at high dynamic range, detect small-molecule binding, and mass-measure polypeptides, glyco- and lipoproteins. These capabilities enable us, using concepts firmly based in physical chemistry, to quantify the molecular mechanisms of processes as diverse as homo- and hetero-oligomeric protein assembly, amyloidogenic protein aggregation and actin polymerisation . Our results illustrate how single molecule mass imaging provides access to protein dynamics and interactions and introduces a third, light-based approach to measuring mass in addition to the historical mechanical and spectrometric methodologies.
About the Speaker
Philipp Kukura read Chemistry at St Hugh’s College Oxford until 2002 and did a PhD at the University of California, Berkeley with Rich Mathies in ultrafast spectroscopy before moving to ETH Zurich to work with Vahid Sandoghdar in nano-optics. After returning to Oxford initially as an EPSRC Career Acceleration Fellow in 2010, he was elected to a tutorial fellowship at Exeter College in 2011 and promoted to Full Professor in 2016. Recent awards include those by the Royal Society of Chemistry (Harrison-Meldola 2011 and Marlow 2015), the European Biophysical Society Association (Young Investigator Medal 2017), a Royal Society Wolfson Research Merit Award (2018) and selection as a UK Blavatnik Award Finalist (2018). PK leads an interdisciplinary research group that focusses on the development and application of new optical methodologies to study biomolecular structure, dynamics and interactions, their role in controlling protein function and resulting avenues for therapeutic intervention.
1. Young G, Hundt N, Cole D, Fineberg A, Andrecka J, Tyler A, Olerinyova A, Ansari A, Marklund EG, Collier MP, Chandler SA, Tkachenko O, Allen J, Crispin M, Billington N, Takagi Y, Sellers JR, Eichmann C, Selenko P, Frey L, Riek R, Galpin MR, Struwe WB, Benesch JLP, Kukura P. Quantitative mass imaging of single biological macromolecules. Science 2018 360: 423-327