Biomedical Center (BMC) provides deep insights into the nanoworld

The STED microscope can resolve structural details that are less than 50 nanometers apart within cells. This super-resolution image of a HeLa cell reveals the pores in the nuclear membrane (green), individual protein molecules (red) and cytoskeletal fibers (white). Source: Leica Microsystems

It is quite unusual for Nobel Laureates in Chemistry to receive the Prize for essentially technical innovations. But the novel methods of super-resolution fluorescence microscopy for which the prize was awarded in 2014 have indeed led to a revolution in the visualization of biological structures at the subcellular level.

Among the most fascinating pieces of equipment in LMU’s young Biomedical Center (BMC) is an instrument which implements one of the award-winning imaging techniques – the STED microscope. The acronym stands for “stimulated emission depletion”, a method of improving optical resolution by quenching all fluorescence outside the center of the illuminated area. As a result, the scanning STED microscope achieves a resolution of below 50 nanometers (nm), which is over four times better than that of the best conventional optical microscope. This breakthrough opened up a new era in light microscopy, because it overcame a barrier – the so-called diffraction limit – which had long been regarded as insurmountable. “With new instruments like this, it has become possible to study biological processes which were previously beyond the limits of optical microscopy,” says Dr. Steffen Dietzel, who heads the new Core Facility Bioimaging at the BMC. The three-dimensional arrangement of much tinier subcellular structures can now be characterized in more detail and with greater precision, providing new insights into their biological function. This will, for instance, enable researchers at the BMC to tackle the question of how the various components that make up the chromatin – the tightly packed complex of genomic DNA and proteins found in the cell nuclei of all higher organisms – are organized in space. This is a crucial issue in molecular genetics, for the precise configuration of the chromatin holds the key to the regulation of the genes encoded in the DNA, which is the central mechanism that determines the function and behavior of every cell type in the body.

The BMC sees its role as that of a center for applied cell research, and this is why imaging technologies play such a central role in its investigations, regardless of whether these studies focus on the dynamic programming of immune cells, nerve cells or stem cells. “Biomedical research is, to a large extent, a highly abstract pursuit, because its practitioners are often forced to deduce the underlying molecular interactions from indirect evidence,” says Professor Peter Becker, Chair of Molecular Biology and Executive Director of the BMC. “This explains why high-resolution microscopy is so important in the field. Because it allows to observe structures within cells, one can check conceptual models against what one can actually see.” The Bioimaging is one of the five Core Facilities to which all in-house researchers have access, and which research groups at other LMU institutes can also call upon.

The Core Facility houses 10 state-of-the-art light microscopes. Five of them, including the STED microscope mentioned above, belong to the class of so-called laser-scanning microscopes, but differ from one another in their detailed specifications and capabilities. Multiphoton microscopes, which use infrared light to excite fluorescence and can therefore probe deeper into tissue than other light microscopes, are also in the line-up. The creation of a Core Facility means that instruments such as the STED microscope, which would be too costly for a single group to acquire and maintain, can be utilized on a shared basis by all BMC researchers. “All our microscopes are optimally equipped and incorporate the latest technology,” Dietzel emphasizes. This enviable state of affairs is in part attributable to the fact that the BMC has entered into a public-private partnership with Leica Microsystems. “Lots of the credit for that must go to the LMUinnovativ program, which first proposed the idea of a bioimaging network and, in so doing, made this latest development possible,” says network coordinator Professor Ulrich Pohl, head of the department in which the new Core Facility Bioimaging is situated. Leica Microsystems, the Wetzlar-based and globally active optics specialist, will continue to support the BMC unit as a European Reference Center, which it will utilize as a Testing and Demonstration Center. In return, the firm will teach BMC staff members in the latest optical technologies and assume responsibility for maintenance and repair of the highly complex instrumentation.

“Our partnership with the BMC makes it possible for us to develop innovations in modern light microscopy, and demonstrate their utility in applied cell biology, in direct collaboration with researchers,” says Dr. Christoph Thumser, who is Director of Marketing for Life Science Research for Europe, Middle East and Africa at Leica Microsystems. “Leica Microsystems has a long tradition of close cooperation with scientists. This is the only way for us to make sure that the solutions we offer meet both the present and future needs of biomedical researchers.“ “Our strategic partnership with Leica Microsystems will stimulate communication between leading microscope developers and a particularly demanding group of users,” says Becker. “Both sides will certainly benefit from this exemplary form of dialog.”

The Core Facility Bioimaging opens officially on February 17th with a scientific symposium, which has been organized jointly by both partners in the cooperation.