At the forefront with Nobel Prize winning microscope – University of Copenhagen

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03 November 2014

At the forefront with Nobel Prize winning microscope

Nanoscopy

The invention of super resolution microscopy won this year’s Nobel Prize in Chemistry - a revolutionary technique that literally has made the impossible possible. Thanks to a group of researchers at the Center for Advanced Bioimaging (CAB) the University of Copenhagen is right at the forefront of this revolutionary field.

Worldwide a growing community of scientists takes advantage of the novel possibilities of super resolution microscopy. Already in early 2012, Center for Advanced Bioimaging (CAB) at the University of Copenhagen acquired this groundbreaking instrument and the center's proactive investment and many hours in front of the advanced equipment have already led to exciting discoveries and publications.

Super resolution image of tiny cellulose fibers on the surface of a fraction of a skin cell of an onion.  (Liesche J, Ziomkiewicz I, Schulz A (2013))

Unthinkable even a few years ago

Head of CAB, Professor Alexander Schulz is one of the initiators of CAB’s purchase of the super resolution microscope. He is also one of its most proficient users. Alexander Schulz tells:

 “With this microscope we are right at the border of what is imaginable. We have observed hitherto unknown structures within cells and seen how individual proteins interact with each other. All of this was absolutely unthinkable even a few years back.”

It is a tedious process to acquire such a sophisticated instrument, get it installed and learn how to use it efficiently. Luckily, at CAB the establishment phase went well and already for more than two years, a dedicated group of researchers is using it to observe tiny details within plant cells and cells from humans. Their efforts have already led to exciting discoveries and resulted in several publications.

From microscopy to nanoscopy

With the super resolution microscopy technology scientists can monitor individual molecules inside cells with a resolution down to 20-30 nanometers. In fact, one may say that microscopy has turned into nanoscopy.

Up until recently, scientists thought that optical microscopes had a definite scientific limitation: that they would never yield a resolution better than 200 nanometers. This year's chemistry laureates used innovative mathematical and chemical tricks to by-pass this limitation - and today scientists are able to see things with up to a tenfold-improved resolution.

It is no simple task to use a super resolution microscope. Firstly, you need thorough knowledge of the apparatus and of what could go wrong. You need to know if the thing you observe is really what you think it is - and not some tiny dust particles on, say, the lenses. Secondly, it is crucial to understand how to interpret the results; here advanced mathematical and statistical calculations play a big role. And not the least, you need to be well versed in the underlying cell biology before the images make sense and may be deduced correctly.

CAB's super resolution microscope is located at the Department of Plant and Environmental Sciences, Fredericsberg Campus, University of Copenhagen.

Looking deep into cells

Iwona Ziomkiewicz is a third year PhD student at CAB. Her PhD project involves many hours in front of the super resolution microscope where she studies a specialized type of cells that carry sugars around in plants, the so-called sieve tube elements.

Iwona Ziomkiewicz is fascinated by the possibilities of super resolution microscopy and all the tiny details she can observe, but she is also well aware that she cannot use it for everything.

“You don’t use super resolution if you want to look at a whole cell. You have to know what you want to zoom in on. For example, you can use it to look inside the cell’s nucleus to find out where a certain gene is located on the DNA. You have to know exactly what you want to find, or you have no chance finding it,” Iwona Ziomkiewicz explains.

Publications

Data found by the use of super resolution microscopy by Alexander Schulz, Iwona Ziomkiewicz, Johanens Liesche and other CAB researchers have already resulted in scientific publications and several more are in the pipeline. Here follows a list of journal papers where the authors use data collected by the super resolution microscope at CAB:

Liesche J, Ziomkiewicz I, Schulz A (2013) Super-resolution imaging with Pontamine Fast Scarlet 4BS enables direct visualization of cellulose orientation and cell connection architecture in onion epidermis cells. BMC Plant Biology 13: 226

Linnik O, Liesche J, Tilsner J, Oparka KJ (2013) Unraveling the structure of viral replication complexes at super-resolution. Frontiers in plant science 4: 6-6

Bjerregard B, Ziomkiewicz I, Schulz A, Larsson LI (2014) Syncytin-1 in differentiating human myoblasts: relationship to caveolin-3 and myogenin. Cell Tissue Res 357:355-62

Walter AM, Kurps J, de Wit H, Schöning S, ToftBertelsen TL, Lauks J, Ziomkiewicz I, Weiss AN, Schulz A, Fischer von Mollard G, Verhage M, Sørensen JB (2014) The SNARE protein vti1a functions in dense‐core vesicle biogenesis. Embo Journal 33: 1681-1697