Ever since physicist Ernst Abbe phrased the “diffraction limit” for optical microscopy in 1873, it has been a dogma that objects below the size of half the wavelength of light could not be resolved by light microscopy. Electron microscopes undercut this limit by using radiation of shorter wavelengths, but at the expense of contrast and viability of specimens.
Meanwhile, the boundaries of light microscopy were tweaked by physicists and biologists alike. The invention of fluorescent microscopy allowed the study of live specimens. By tagging cellular components with fluorescent molecules, biologists were able to explore the structure and function of biological processes. The development of super-resolution (SR) fluorescence microscopy unlocked the access to spatial resolutions beyond the diffraction limit of visible light. One of these techniques was developed in the lab of Stefan Hell at the Max Planck Institute for Biophysical Chemistry. STED (stimulated emission depletion) microscopy separates neighboring fluorescing molecules by switching them on and off one after the other so that they emit fluorescence sequentially. It achieves a resolution of about 20-30nm and earned Stefan Hell a Nobel Prize in Chemistry in 2014.
MINFLUX achieves nanometer resolution
However, achieving resolutions at the molecular level - that is around 1nm - is challenged by multiple trade-offs between spatial and temporal resolutions, depth of observation and photo toxicity. In 2016, Francisco Balzarotti and colleagues in Stefan Hell’s lab developed MINFLUX (MINimal emission FLUXes), a localisation technique that merges concepts of SR with information theory. It achieves nanometer resolution in three dimensions with unrivalled spatio-temporal resolution. However, MINFLUX is not fast enough to directly observe molecular processes within living cells.
In January 2020, Francisco Balzarotti will take up a position as Group Leader at the IMP, where he will join a strong community of scientists pushing the limits of microscopy. He will develop a platform that enables the capabilities of MINFLUX in a high-throughput manner for entire cells and tissue in living conditions. To achieve this goal, he will develop complementary systems for high throughput imaging and for tracking of molecular dynamics with unrivalled performance. “The performance of fluorescence imaging and tracking will progress by orders of magnitude in the years to come, signaling yet another revolution for optical nanoscopy”, Balzarotti says. His project will be supported by funds from the European Research Council through an ERC Starting Grant, worth over 1.7 million Euro, that was announced earlier today.
About ERC Starting Grants
ERC Starting Grants are awarded to early-career researchers with two to seven years of experience since completion of the PhD and a scientific track record showing great promise. The research must be conducted in a public or private research organisation located in one of the EU member states or associated countries. The funding (maximum 2.5 million Euro per grant, including up to 1 million Euro to cover extraordinary costs) is provided for up to five years. At the IMP, there are currently 11 ERC awardees among a faculty of 15. Another Starting Grant in this call will go to Alejandro Burga of IMBA, resulting in two fresh ERC Grants for the Vienna BioCenter.
About Francisco Balzarotti
Francisco Balzarotti was born in Argentina and studied engineering at the University of Buenos Aires. For his dissertation, he worked on super-resolution techniques for the optical fabrication of nanostructures. After obtaining his PhD in 2012, he joined the Max Planck Institute for Biophysical Chemistry in Göttingen as a postdoctoral researcher. Working in the group of Nobel Laureate Stefan Hell, he focused on the development of super-resolution microscopy techniques. His innovations earned him a number of research awards, among them the “Top Ten Breakthrough of 2017” by Physics World.