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Theory of Living Matter Group


7th General Meeting

General information

The topic of this meeting will be super-resolution (SR) Microscopy, a class of new technologies that are capable of providing light image resolutions down to the nanometer regime, breaking the traditional physical barrier of half the light wavelength (around 200nm). In this TLM meeting we will learn how this is possible. Our speakers in this meeting will be Prof Clemens Kaminski, from the Department of Chemical Engineering and Biotechnology, and Dr Ricardo Henriques from the Laboratory of Molecular Cell Biology, UCL, London. They will give an introduction to the underlying physical and theoretical principles behind some super-resolution techniques and will also show some experimental applications where the information gain of SR microscopy is essential.

After the talk there will be a drinks reception with snacks and plenty of time for informal discussions.

Registration closed.

Tuesday, 8th March 2016, 5pm

Main lecture theatre, Sainsbury Laboratory
Bateman Street, Cambridge CB2 1NN

Directions: The Sainsbury Laboratory Cambridge University is located in Cambridge University Botanic Garden and can be accessed via Bateman Street. Note that the entrance to the Sainsbury Laboratory is rather hidden in the backyard of an arts school. There will be signs and people waiting to guide the way.


“Optical Nanoscopy to study molecular mechanisms of disease”

Clemens Kaminski, University of Cambridge

The self-assembly of proteins into ordered macromolecular units is fundamental to a variety of diseases. For example, in Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), proteins that are usually harmless are found to adopt aberrant shapes; one says they ‘misfold’. In the misfolded state the proteins are prone to aggregate into highly ordered, toxic structures, called protein amyloids and these make up the insoluble deposits found in the brains of patients suffering from these devastating disorders. Virus particle assembly is another example of a protein self-assembly process associated with disease. A key requirement to gain insights into molecular mechanisms of disease and to progress in the search for therapeutic intervention is a capability to image the protein assembly process in situ i.e. in cellular models of disease. In this talk I will give an overview of research to gain insight on the aggregation state neurotoxic proteins in vitro (1), in cells (2, 3) and in live model organisms (4). In particular we wish to understand how these and similar proteins nucleate to form toxic structures and to correlate such information with phenotypes of disease (3). I will show how direct stochastic optical reconstruction microscopy, dSTORM, and multiparametric imaging techniques, such as spectral and lifetime imaging, are capable of tracking amyloidogenesis in vitro, and in vivo, and how we can correlate the appearance of certain aggregate species with toxic phenotypes of relevance to PD and AD (5). Finally I will show how superresolution gives insights into the self-assembly process of viral particles at a resolution that rivals electron microscopy techniques (6).
(1) 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
(2) 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)
(3) Esbjörner, E.K., Chan, F., Rees, E., Erdelyi, M., Luheshi, L.M., Bertoncini, C.W., Kaminski, C.F., Dobson, C.M., and Kaminski Schierle, G.S., “Direct Observations 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 & Biology (2014).
(4) Kaminski Schierle GS, Bertoncini CW, Chan FTS, van der Goot AT, Schwedler S, Skepper J, Schlachter S, van Ham T, Esposito A, Kumita JR, Nollen EAA, Dobson CM, Kaminski CF, "A FRET sensor for non-invasive imaging of amyloid formation in vivo", ChemPhysChem, 12(3), 673–680, (2011)
(5) 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.
(6) Laine R F. Albecka A, van de Linde S, Rees E J, Crump C M, Kaminski C F, "Structural analysis of herpes simplex virus by optical super-resolution imaging." Nature Communications (2015), 6:5980

“Democratising High-Speed Live-Cell Super-Resolution Microscopy”

Ricardo Henriques, University College London

DNA, RNA and protein, part of the central molecules of biology, typically exist at dimensions of a few nanometers, well beyond the resolving power of conventional fluorescent microscopy (~300 nm). Super-resolution microscopy techniques hold to date the record in resolving power for light microscopy. However, despite significant progress, high-speed live-cell super-resolution studies remain limited to specialised optical setups, generally requiring intense phototoxic illumination. In this talk I will introduce how super-resolution is revolutionising cell biology, achieving the potential to resolve and identify cellular elements never seen before and describe a new super-resolution approach we have developed, enabling super-resolution in modern widefield or TIRF microscopes using conventional fluorophores such as GFP. With this novel method we demonstrate super-resolution live-cell imaging over timescales ranging from minutes to hours, using sample illumination orders of magnitude lower than methods such as PALM, STORM or STED.