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Watching proteins at work

Optical microscopy is going through a revolution, says Dorus Gadella.  It is providing more and more detailed data on biomolecules. A next step: integration of the field into bioinformatics.

Dorus Gadella (Photography Thijs Rooimans)

“Some people watch our bioimaging movies open-mouthed”, tells Dorus Gadella. “For the first time people can actually see single molecules in a living cell.” Gadella has been working in the field of optical microscopy for nearly twenty years, and strongly feels that harvesting times are here. “It feels like we are on a kind of exploratory expedition.Compare it with people going to Mars. We are looking at a landscape that has never been seen before: the cell, and learn how molecules make-up life.”

Living cells

The excitement that Gadella feels, is the result of several recent scientific developments. It is now possible to label almost any protein of choice with a fluorescent probe, making it possible to track it in a living cell or organism. It is also possible to label more than one protein using different labels. And not only the whereabouts of a protein may be detected, with special labels it is also possible to see if a protein is in its active conformation: at work.

Another advancement is optogenetics. Scientists are able to add light-sensitive probes to particular proteins which makes it possible to switch them ‘on’ and ‘off’ in a living cell using light. Using optogenetics biologists have been able to close ion channels in C. Elegans with UV-light. Optogenetics allows more accurate and robust information about proteins’ functions than knock-outs, argues Gadella. “Using optogenetics you can initiate highly local and sudden changes in a living cell and study the immediate consequences.”

Besides advances in fluorescent labeling techniques, the resolution in bioimaging has been shattered. Gadella: “Until recently we were looking at large ‘blurs’ but suddenly the resolution has improved by a 20-fold.” Combined with advanced digital imaging analysis and automation in parallel microscopy huge steps forward have been made in bioimaging.

Bioinformatics

Gadella wants to integrate bioimaging and bioinformatics. Hereto optical microscopy data needs to be linked with, for example, proteomics and genomics data. An interesting problem to be resolved is the different format of data that bioimaging provides: pictures, or -in informatics terms- pixels.  “That will be a challenge”, admits Gadella. “But I’m convinced that it is worthwhile and useful.”

Dorus Gadella is professor in Molecular Cytology (Swammerdam Institute for Life Sciences , UvA) and founder/director of the Centre for Advanced Microscopy (CAM in Amsterdam. He presented a keynote lecture entitled ‘The microscopy and bioimaging revolution: seeing is believing’. An extended interview with Dorus Gadella will be published in the November 2012 issue of Interface.

Author: Marga van Zundert