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After graduating from high school in 1985, Kornath began studying chemistry at the University of Dortmund, which he completed in 1989. He continued his academic career with a diploma thesis under the supervision of Professor Rolf Minkwitz on the chemistry of mercaptosulphonium salts, which he successfully completed in September 1990.

In 1993, he received his doctorate with a thesis on the chemistry of chalcogen and picogenium salts and triphenylsilysulphanes under Professor Minkwitz in Dortmund.

This was followed by a post-doctorate at the University of Alabama in Tuscaloosa, USA. Kornath then returned to Germany and worked as a research assistant at the University of Dortmund from January 1995 to September 2000. During this time, he also spent three months at the University of California in Los Angeles.

Andreas Kornath habilitated in Dortmund in 2000 with a thesis on the structural elucidation of ligand-free metal cluster reactivity of bare anions. Kornath subsequently worked there as a lecturer and later as a senior research associate in the Department of Inorganic Chemistry. Between April 2005 and July 2006, he held professorships in inorganic chemistry at the universities of Rostock and Munich. From August 2006, he worked as a university lecturer in Dortmund before taking up a professorship in inorganic chemistry at LMU in April 2007, which he held until the end of his life.

Kornath's research focused on extremely strong acids, also known as superacids. He was particularly interested in the associated phenomena, which are important not only on Earth but also in interstellar space.

Acid strength plays a decisive role in numerous chemical reactions in biological and technical processes. Superacids reach the highest known acidities and therefore offer enormous potential for the investigation of highly reactive intermediates as well as for applications in technical processes.

Andreas Kornath's scientific work, characterized by his commitment to research and teaching, has significantly enriched the world of inorganic chemistry. His legacy will endure through his numerous publications and the generations of chemists he trained and inspired.

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Cockayne syndrome is a severe autosomal recessive disorder caused by defective DNA repair mechanisms. People with the disease have much reduced life expectancy and suffer from facial deformities; growth failure; neurological, cognitive, and sensory impairments; bone, joint, and muscle deformities; kidney problems; and premature aging. Like xeroderma pigmentosum (XP), Cockayne syndrome (CS) is a disease where elements of nucleotide excision repair (NER) do not work properly. The purpose of this repair mechanism is to remove DNA damage caused by ultraviolet (UV) light, chemicals, and various other environmental factors.

Researchers from the group of biochemist Professor Julian Stingele from LMU’s Gene Center Munich have now uncovered important details about the role of the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. These genes encode two enzymes associated with DNA repair. The results of their work have been published in the journal Nature Cell Biology. “Our data point to a new, previously unknown function of these two genes and their gene products in the repair of covalent DNA-protein interactions in the course of transcription,” reports Stingele, referring to the cytotoxic, biologically undesirable crosslinking of proteins to DNA.

An obstacle for transcription News Colliding ribosomes activate RNA repair Read more

In collaboration with researchers from the University of Cambridge, the scientists demonstrated that DNA-protein crosslinks present a physical obstacle to further transcription. Arresting transcription brings CS proteins to the blockade sites. “Our results indicate that CSB and CSA then initiate the transcription-coupled repair of the toxic DNA-protein crosslinks,” says Stingele. “This previously unrecognized cellular function of CS proteins leads to the marking of the DNA damage – and thence to its enzymatic breakdown.”

The study also revealed that this newly discovered function of CS proteins works independently of classic TC-NER (transcription-coupled nucleotide excision repair) enzymes, which are deployed, among other things, for repairing DNA damage caused by UV light – and the absence of which leads to xeroderma pigmentosum. “The fact that CS proteins have additional functions is noteworthy. This discovery could help to explain the pathological differences between xeroderma pigmentosum and Cockayne syndrome,” says Stingele. CS is a more severe and more multifaceted disorder than XP, with complex and incompletely understood causes. As their next step, Stingele’s research group plans to decode the exact process of CS-protein-mediated repair.

Christopher J. Carnie et al.: Transcription-coupled repair of DNA-protein crosslinks depends on CSA and CSB. Nature Cell Biology 2024

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Here are the key points of this new RSC Platinum model:

• Duration 4 years
• permanent read access to the content published in the entire RSC journal portfolio during the contract period
• unlimited OA publication rights (CC-BY as standard license) for LMU Corresponding Authors in all hybrid and gold OA journals
• The Corresponding Author is assigned to LMU exclusively via the e-mail address (@....lmu.de, @....uni-muenchen.de, @....cup.uni-muenchen.de, or similar)

Further information and the current list of titles on which the agreement is based can be found here.

If you have any questions or problems in connection with the RSC agreement, please contact your subject librarian:

Dr. Andreas Will
andreas.will@ub.uni-muenchen.de
+49 89 2180 77065

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The University Day is an LMU event in which a group of selected high school students from grammar schools in Upper Bavaria visit the university's various faculties over the course of a semester. On December 8, 2023, the group visited the Departments of Chemistry and Biochemistry.

The pupils learned about our combined chemistry/biochemistry degree program and our teaching degree program, took part in a lecture and enthusiastically carried out their own experiments in various laboratories.

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Processes within our bodies are characterized by the interplay of various biomolecules such as proteins and DNA. These processes occur on a scale often within a range of just a few nanometers. Consequently, they cannot be observed with fluorescence microscopy, which has a resolution limit of about 200 nanometers due to diffraction. When two dyes marking positions of biomolecules are closer than this optical limit, their fluorescence cannot be distinguished under the microscope. As this fluorescence is used for localizing them, accurately determining their positions becomes impossible.

This resolution limit has traditionally been overcome in super-resolution microscopy methods by making the dyes blink and turning their fluorescence on and off. This temporally separates their fluorescence, making it distinguishable and enabling localizations below the classical resolution limit. However, for applications involving the study of rapid dynamic processes, this trick has a significant drawback: blinking prevents the simultaneous localization of multiple dyes. This significantly decreases the temporal resolution when investigating dynamic processes involving multiple biomolecules.

Under the leadership of LMU chemist Professor Philip Tinnefeld and in cooperation with Professor Fernando Stefani (Buenos Aires), researchers at LMU have now developed pMINFLUX multiplexing, an elegant approach to address this problem. The team recently published a paper on their method in the journal Nature Photonics. MINFLUX is a super-resolution microscopy method, enabling localizations with precisions of just one nanometer. In contrast to conventional MINFLUX, pMINFLUX registers the time difference between the excitation of dyes with a laser pulse and the subsequent fluorescence with sub-nanosecond resolution. In addition to localizing the dyes, this provides insights into another fundamental property of their fluorescence: their fluorescence lifetimes. This describes how long, on average, it takes for a dye molecule to fluoresce after it is excited.

Functional architecture that builds itself

“The fluorescence lifetime depends on the dye used,” explains Fiona Cole, co-first author of the publication. “We exploited differences in fluorescence lifetimes when using different dyes to assign the fluorescent photons to the dye that emitted without the need for blinking and the resulting temporal separation.” For this purpose, the researchers adapted the localization algorithm and included a multiexponential fit model to achieve the required separation. “This allowed us to determine the position of multiple dyes simultaneously and investigate rapid dynamic processes between multiple molecules with nanometer precision,” adds Jonas Zähringer, also co-first author. The researchers demonstrated their method by accurately tracking two DNA strands as they jumped between different positions on a DNA origami nanostructure, as well as by separating translational and rotational movements of a DNA origami nanostructure and by measuring the distance between antigen-binding sites of antibodies. “But this is just the beginning,” says Philip Tinnefeld. “I am certain that pMINFLUX multiplexing, with its high temporal and spatial resolution, will provide new insights into protein interactions and other biological phenomena in the future.”

INFO: Fiona Cole, Jonas Zähringer, Johann Bohlen, Tim Schröder, Florian Steiner, Martina Pfeiffer, Patrick Schüler, Fernando D. Stefani & Philip Tinnefeld: Super-resolved FRET and co-tracking in pMINFLUX. Nature Photonics 2024

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Molecular reaction networks that reveal the various reaction possibilities of a system are of vital importance for chemistry and biochemistry. The molecular origins of life are a prime example of branched networks. We need only recall the famous “primordial soup” experiment (Miller-Urey experiment) of 1953 on the emergence of organic molecules in the Earth’s early atmosphere or consider the formation of molecules in interstellar space. Understanding, predicting, and ultimately calculating such reaction networks is a highly complex task. With the development of a so-called hyperreactor, the team led by Christian Ochsenfeld, Professor of Theoretical Chemistry at LMU, is pursuing this ambitious goal.

Using the tools of theoretical chemistry, it is possible to simulate such reaction networks. A key challenge is presented by the complexity of the potential energy hypersurfaces of chemical systems, with numerous minima and connecting saddle points. The latter constitute energy barriers which a chemical reaction must overcome. Simplifying matters, we can picture this potential energy hypersurface as a mountainous terrain, where various molecules or structures correspond to the valleys and the energy barriers to be overcome are represented by the mountains.

The difficulty posed by the energy barriers, which are often very high, were circumvented in early approaches by means of simulation under periodic contractions (pressure) and very harsh reaction conditions such as extremely high temperatures to induce chemical reactions. However, this has also led to unrealistic reactions and fragmentations. By contrast, the new hyperreactor from the Ochsenfeld group enables the study of complicated reaction networks under mild conditions. To this end, periodic contractions of the molecular system are coupled with the exploration of chemical space on smoothed potential energy surfaces.

Sample applications of the hyperreactor – such as the calculation of nonenzymatic DNA nucleoside synthesis, which is being experimentally researched in the group led by Oliver Trapp, Professor of Organic Chemistry at LMU, or the synthesis of glycinal, acetamide, and carbamic acid in interstellar ices at -263°C – are yielding initial insights into the new computational possibilities. Particularly when combined with new, almost 1,000 times faster quantum chemical methods, which were also developed in Ochsenfeld’s research group, the hyperreactor opens up new perspectives for the exploration of complex reaction networks and for research into a wide variety of chemical and biochemical synthesis pathways.

Alexandra Stan-Bernhardt, Liubov Glinkina, Andreas Hulm, Christian Ochsenfeld: Exploring Chemical Space Using Ab Initio Hyperreactor Dynamics; ACS Central Science 2024

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The synthesis of proteins in the cell is a key process of life. By this means, the genetic code of the genome is translated into the amino acid sequence of proteins. The process is complex – and has been studied in detail for decades.

Protein biosynthesis is performed by special molecular machines, ribosomes, which consist of a large and small subunit. At the end of protein biosynthesis, these protein factories have to be broken up into their individual parts (recycled), so that they are ready for the next round of translation.

Now a team led by Professor Roland Beckmann, Dr. Thomas Becker, and Ivan Penchev from LMU’s Gene Center Munich, working in collaboration with researchers at Stanford University led by Professor Ron Kopito, have shown how the recycling of ribosomes at the so-called endoplasmic reticulum (ER) functions. In the process, they discovered the role of an enzyme, a special E3 ligase that joins a small protein modification called UFM1 to the large ribosomal subunit, as a key mechanism of recycling. An account of their investigations has been published in the prestigious journal Nature.

Detailed insights into the recycling of ribosomes

Ribosomes are usually found floating within the cytoplasm. “Here we know precisely how the recycling works,” says Becker. Sometimes, however, they are located at the endoplasmic reticulum, a continuous cell-wide membrane network.

Although many proteins originate in the cytosol, they subsequently have to be brought to other organelles, such as mitochondria, chloroplasts, and many more. If a protein is synthesized at the ER membrane, the whole translation machinery docks to the ER membrane. This is accomplished with the aid of a protein-conducting channel (SEC61), which is able to transport proteins across the membrane or insert them into the membrane during synthesis.

After completion of the translation, there is a further recycling step, which is specific to the ER membrane. Namely, the large subunit of the ribosome has to be detached again from the protein-conducting channel. Beckmann’s team has now demonstrated how this substep works: When the translation has finished, the E3 ligase recognizes the large subunit of the ribosomes. “It places – figuratively speaking – a small wedge, the protein UFM1, at the large subunit,” explains Becker. "This produces a stable complex out of the modified 60S subunit and the E3 ligase. Simultaneously, it causes the large subunit to detach from SEC61. This is a very important step to ensure that the large subunit is returned to the cytosol and available for the next round."

Paul A. DaRosa, Ivan Penchev, Samantha C. Gumbin, Francesco Scavone, Magda Wąchalska, Joao A. Paulo, Alban Ordureau, Joshua J. Peter, Yogesh Kulathu, J. Wade Harper, Thomas Becker, Roland Beckmann & Ron R. Kopito: UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER. Nature 2024