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Nobel prize awarded for optical super-resolution microscopy

The inventors of single molecule localisation and stimulated emission depletion (STED) super-resolution microscopy were today honoured with the Nobel prize for chemistry. One of the key applications of super-resolution imaging, pioneered by Professor Clemens Kaminski, (a CDT Supervisor at Cambridge) and mentioned by the Nobel Assembly, is the study of protein aggregation reactions in the context of neurodegenerative diseases.
Nobel prize awarded for optical super-resolution microscopy

Nanoscopy uncovers toxic protein amyloids


Super-resolution microscopy is an active area of research in the IPES CDT. The Laser Analytics Group, led by centre supervisor Professor Clemens Kaminski, were the first to apply single molecule localisation microscopy, for the development of which Dr. Eric Betzig and Professor William Moerner were honoured today, in the study of protein aggregation reactions that cause neurodegeneration. The technique was first described by the group in the Journal JACS in 2011 and visualises with unprecedented resolution and within neurons the morphology of protein aggregates of proteins causing Alzheimer's disease. More recently in a paper published in the Journal JCB, and widely commented on in the news, super-resolution microscopy was used to demonstrate how the protein tau, a hallmark protein in Alzheimer's Disease,  aggregates and propagates between cells.

This research into neurodegeneration with optical nanoscopy, pioneered by the Laser Analytics Group, was cited by the Nobel assembly as a key application for super-resolution microscopy during their announcement. The group continues to research in this area and continue to develop algorithms and techniques for single molecule localisation.

The CDT continues to work in this area. Centre student Nathan Curry, working with Dr. Pierre Mahou and supervised by Professor Kaminski, has developed a STED microscope (based upon the work of prize winner Professor Hell), to compliment the fluorescence nanoscopy techniques already applied to the study of neurodegenerative diseases.  Centre student Na Yu, also in this group and working with Dr. Claire Michel, is developing microfluidic devices compatible with both super-resolution techniques.

For more information about optical nanoscopy please see the Laser Analytics Groups recent features on the Nobel Prize announcement and on super-resolution activities within the group.

Relevant publications

Kaminski Schierle GS, van de Linde S, Erdelyi M, Esbjörner EK, Klein T, Rees E, Bertoncini CW, Dobson CM, Sauer M, and Kaminski CF, "In Situ Measurements of the Formation and Morphology of Intracellular ß-Amyloid Fibrils by Super-Resolution Fluorescence Imaging", J. Am. Chem. Soc., 133 (33), pp 12902–12905, (2011). DOI | pdf | summary

Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P, Mandelkow E, Mandelkow E-M, Kaminski CF, Kaminski Schierle GS, "Extracellular Monomeric Tau is Sufficient to Initiate the Spread of Tau Pathology", J. Biol. Chem. (2014), 289: 956-967. DOI | pdf | summary

Pinotsi D, Büll AK, Galvagnion C, Dobson CM, Kaminski-Schierle GS, Kaminski CF, "Direct Observation of Heterogeneous Amyloid Fibril Growth Kinetics via Two-Color Super-Resolution Microscopy," Nano Letters (2013), 14 (1), 339–345 DOI | pdf | summary

Fritschi S K, Langer F, Kaeser S A, Maia L F, Portelius E, Pinotsi D, Kaminski C F, Winkler D T, Maetzler W, Keyvani K, Spitzer P, Wiltfang J, Kaminski Schierle G S, Zetterberg H, Staufenbiel M, Jucker M, "Highly potent soluble amyloid-β seeds in human Alzheimer brain but not cerebrospinal fluid," Brain (2014). awu255. DOI | pdf | summary

Esbjörner E K, Chan F, Rees EJ, Erdelyi M, Luheshi LM, Bertoncini CW, Kaminski CF, Dobson CM, Kaminski-Schierle GS, "Direct Observations of the Formation of Amyloid β Self-Assembly in Live Cells Provide Insights into Differences in the Kinetics of Aβ(1–40) and Aβ(1–42) Aggregation," Chemistry and Biology (2014)  DOI |pdf | summary

Kaminski C F, Pinotsi D, Michel C H, Kaminski Schierle G S, "Nanoscale imaging of neurotoxic proteins", SPIE NanoScience+ Engineering (2013), 91690N--91690N. DOI | pdf | summary