The nucleus in view

Delft Outlook, July 2010

If you ask Dr David Grünwald what his specialism is, he will answer, “Visualising molecules within the nucleus of a living cell.” It takes a few moments for the significance of this simple statement to sink in.

Click image for .pdf downloadYou can’t see molecules with an optical microscope, can you? Surely they’re far too small? Seeing molecules within a living cell could enable you to watch various processes of life as they happen. Apparently, it is indeed possible. Through observation, Grünwald has established that it takes 200 milliseconds for an RNA molecule to permeate the cell wall on its way out, while the average protein finds its way in within 5 to 10 milliseconds. “The best part was seeing how an RNA molecule would try various nuclear pores one after the other. It waits for a second or so at one, then moves on until it finds a pore that will actually let it in.”
Grünwald (34) can tell fascinating stories about the world which only a very few people, himself included, can make visible: the living complex that is a cell. Having studied law in Frankfurt for one year (“I wanted to do something good for mankind, but studying law is not easy when you’re dyslexic”), he went on to study physics and was then introduced to biophysics. “How does life work? Not just as a description, but in the quantitative sense. How does a cell function and what principles keep life going? That question grabbed me and has never let me go.” Since then, his glittering scientific career has seen him working at institutes of biophysics, biochemistry, molecular biology and medicine. After four years as a postdoctoral researcher at the Albert Einstein College of Medicine in New York, Grünwald decided it was time to return to physics.
With the help of technicians and PhD students, he is now building his own microscope, which is specially designed to follow individual molecules. The crucial factor is ensuring the maximum possible light. The microscope, which is actually an open arrangement with lasers, a large-aperture lens, a colour-separation mirror and two ultra-sensitive cameras, will enable him to observe the interaction between various molecules with a precision of up to 30 nanometres. Fluorescence labelling can then be used to determine whether a virus is able to penetrate a nuclear pore, or the point at which a particular drug binds itself to the cell and how this affects the functioning of that cell. “All this happens within milliseconds,” Grünwald says. “These processes are taking place in all our cells. We can see them happening. Not just on the outside of the cell – its ‘envelope’ – but in the nucleus itself.”