Entries in ExM (1)

Monday
Apr042016

I see, therefore I am

Vision is a fascinating sense. In some way, it must also be our favorite one. We just have a very strong desire to see things. A beautiful sight, be it a landscape, a piece of art or a person, can make us happy. As a consequence, we have whole industries producing visual arts, building beautiful buildings,and bringing us to places that look nice.

 

Vision is also our go-to input pathway to help us learn and understand complex things: Looking at a switching circuit will be tremendously helpful to understand a complicated electronic device. Drawing out the mechanism of a chemical reaction will help us grasp what is going on in the atomic world.

However, vision quickly runs into its limitations when we try to satisfy our thirst for understanding living systems. The resolution that our eyes provide just isn’t sufficient to dive down into the molecular world, which is the current level at which we try to understand unanswered questions in medicine and life sciences. Thus, tools that function as an extension of our visual sense, by surpassing limits of, e.g. resolution or visibility, enabled many scientific breakthroughs in the past century.

When I say this, I am thinking about X-ray diffraction, Roentgen, CT, MRI and PET-imaging, as well as microscopy. The latter stands out in a way, because it is the oldest and most fundamental technique. It utilizes the very same tools our own eye uses for magnification: lenses. Microscopes were the door opener for both recognizing and understanding cellular and sub-cellular structures.

The continuous improvement of microscopy by utilization of advances in physics and computation has yielded incredibly powerful machines. One pinnacle of this development is certainly super-resolved fluorescence microscopy, which has been awarded with the Nobel Prize in Chemistry for 2014. Postulated by Ernst Abbe in 1873, light microscopy could never obtain a resolution higher than 0.2 micrometers, based on the wavelength of light. However, with their fearless work, Nobel Laureates Eric Betzig, Stefan Hell and William Moerner could surpass this limit and generate images of nanometer scale structures of neurons.

It is not unlikely that the resolution of microscopes will continue to improve, however, a recent elegant approach from researchers at MIT uses chemistry to achieve superresolution imaging by interpreting microscopy as a two-way-street: On the one hand we can build even more powerful microscopes that surpass the “limitations of physics” to resolve nanoscale structures. On the other hand, we can “expand” our object of interest and then investigate it with standard light-microscopy.[1]

This may sound funny at first, but it is exactly what the group around Ed Boyden has demonstrated in their current work on expansion microscopy “ExM”.[2],[3],[4] Using an expanding polymer, tissue preparations from cultured cells or preparations from the mouse hippocampus could be fixed, blown up, and analyzed with a conventional confocal microscope.

As such, ExM has lowered the activation barrier tremendously for scientists, who seek to image and investigate the biochemical nano-world. It will be exciting to “see” what findings this technique will uncover and help “expand” our knowledge in near future.

 


[1] http://syntheticneurobiology.org/projects/display/57/25

[2] F. Chen, P. W. Tillberg, E. S. Boyden, Science 2015, 347, 543.

[3] http://expansionmicroscopy.org/

[4] https://www.youtube.com/watch?v=-o9-X8TvgFo