Dean: Prof. Dr. Carsten Schmuck †

As examples of the excellent, methodologically diverse and thematically wide-ranging research ongoing within the Faculty of Biology’s research programmes, nine recent highlights are described here. Five of them come from the Medical Biology research area, three from Water and Environmental Research and one from Empirical Educational Research.

The research group of Prof. Stefan Westermann (Medical Biology) investigates the molecular mechanisms of cell division, particularly chromosome segregation. During this process, mechanical forces act to separate the already duplicated chromosomes between two daughter cells. This step is of enormous medical relevance because defective regulation of it may lead to serious diseases such as cancer. A fundamental role in the process of cell division is played by the so-called kinetochore, a multiprotein complex that modulates the binding of microtubules to the centromere of two chromatid sisters, and their consequent separation. The molecular structure of the kinetochore is still largely unknown, however. To gain a better understanding of this complex structure, the Westermann group therefore investigated the kinetochore in yeast: although structurally similar to the human analogue, its function can be more easily characterised using other methods. Applying a new mass-spectrometry method, the researchers obtained a three-dimensional map of the binding positions of the kinetochore’s inner proteins. These cartographic data helped them to better interpret the results obtained in a parallel x-ray analysis, thus leading to the first three-dimensional structure of three protein components of the kinetochore. This work signals an important step forward in the understanding of chromosome segregation and can help to better understand the origin of the abnormal processes that lead to errors in cellular division.

The research group of Prof. Hemmo Meyer (Medical Biology) focuses on the AAA+ ATPase VCP/p97. This protein is a central element of the ubiquitin-proteasome system, which in living cells oversees the degradation of protein complexes. These protein complexes are constantly assembled and disassembled according to cell demand. In cooperation with the research groups of Prof. Andrea Musacchio and Prof. Markus Kaiser (both Medical Biology), the Meyer group was able to demonstrate that VCP/p97 plays an important role in the regulation of the protein-phosphatase 1 (PP1) function. This protein is involved in a number of larger complexes and mediates several different processes, from metabolic reactions to cell division. Upon its biosynthesis, PP1 is inactivated through binding to two inhibitor components, SDS22 and Inhibitor-3. This complex is eventually disassembled by means of VCP/p97, enabling PP1 to interact with other proteins. Such an intricate regulation mechanism probably enables a tighter control of PP1-complex formation, establishing order in the chaos of cellular proteins and protein complexes. The cellular control of the entire process therefore occurs through a new molecular mechanism, which has expanded previous knowledge of VCP/p97 function.

The research group of Dr. Barbara Saccà (Medical Biology) is interested in the implementation of DNA nanotechnology tools to address biological questions. This new and rapidly emerging field of science makes it possible to construct three-dimensional DNA objects of almost any desired size and shape and, most importantly, with programmable nanoscaled features. Such objects could be used, for example, to mimic viral capsids for the transfer of genetic material or proteins. To achieve this ambitious goal, however, much fundamental research is still needed. In a research project in collaboration with the group of Prof. Michael Ehrmann and Prof. Elsa Sánchez-Garcia (both Medical Biology), the Saccà group realised a tubular-shaped DNA origami structure for the efficient encapsulation of a single enzyme in its native form. This opens the way to chemical modification of protein properties (such as stability) using non-covalent supramolecular interactions, and to the use of programmable DNA-encaged proteins as protein carrier systems.

For many years the research group of Prof. Ehrmann (Medical Biology) has been studying a particular class of serine proteases known as HtrA proteases. These proteases display special biochemical properties, such as reversible enzyme activation and inactivation, making them extremely unusual. In addition, several HtrA proteases are of particular medical relevance and interest. New research has shown, for example, that the human HtrA protease HTRA1 seems to play an important role in the pathogenesis of age-related macular degeneration (AMD). Specifically inhibiting this protease may therefore represent a promising chemotherapeutic approach. So far, however, no such inhibitors of this protease have been developed. The Ehrmann group therefore entered into collaboration with the chemical biology group of Prof. Markus Kaiser (Medical Biology) with the aim of developing the first chemical HTRA1 inhibitors. Together, the two research groups were now able achieve their goal by synthesising designed analogues of Ahp-cyclodepsipeptides, a class of natural products originally isolated from cyanobacteria. Their work may thus represent the first step in the development of a new class of powerful AMD chemotherapeutics. In addition, it laid the foundation for further studies to optimise and evaluate clinically usable HTRA1 inhibitors as part of an ERDF “lead market” competition.

In much of contemporary biology research, increasingly sophisticated experimental methods produce increasingly complex data, which makes biological interpretation of the information difficult. The Bioinformatics and Computational Biophysics research group of Prof. Daniel Hoffmann (Medical Biology) develops computational methods that help to reveal new biology in such complex data. However, the computer is not only a versatile tool for the analysis of experimental data, but also enables modelling of complex biological systems and offers a level of insight that is often not accessible with experimental methods. One example is the modelling of eco-evolutionary dynamics with a fundamental question: Why does biological diversity occur and why is it stable? To explore this question, the Hoffmann group developed a model to simulate the dynamics of biological communities that are governed by competitive interactions. The model made it possible to explain the emergence of stable biodiversity and a number of key observations from biological systems by introducing a trade-off between competitive ability and replication rate.

The Biodiversity group led by Prof. Jens Boenigk (Water and Environmental Research) investigates the relation and interplay between biodiversity and ecosystem functions. Its recent research focuses on three main aspects: the shift in species diversity in aquatic ecosystems due to stressor impact, functional diversity in aquatic ecosystems as reflected by metatranscriptomics and metagenomics, and the species distribution pattern on a European scale. In a recent study, the research group succeeded in explaining the role of Cryptophyta as consumers of bacteria in lake plankton communities and proved a hitherto largely neglected direct interaction between the two groups. The results of this study change our understanding of the connectivity and interactions within the microbial food web and thereby of the basis of element flows through ecosystems and ecosystem stability.

Prof. Florian Leese (Water and Environmental Research) works in the field of aquatic ecosystem research. He is particularly known for establishing molecular tools for ecosystem quality assessment and biomonitoring. His pioneering work was also honoured with the 100,000 € Water Resource Award of the Rüdiger Kurt Bode Foundation. In one of these studies Prof. Leese established DNA-based analysis of chironomids (non-biting midges) as an alternative method of water quality assessment. Streams and lakes around the world are affected by climate change and agricultural stressors. Chironomids are hard to determine based on morphology and thus have little or no use as classical indicator species, even though they would be ideally suited as they occur in great abundances in lakes and streams. Prof. Leese’s research group overcame this limitation by using DNA-based tools (“DNA metabarcoding”) to detect indicator species. Thanks to the complex study design, the researchers were able to demonstrate that different stressors clearly impact on chironomid species occurrence. As a result of this research, it will be possible in future to determine the quality of water with DNA analysis of chironomids.

Analysis of the ecophysiological and ecotoxicological effects of extreme volcanogenic CO2 exhalations (mofettes) on plants, fungi, animals, soils and climate is one focus of the research of Prof. Hardy Pfanz (Water and Environmental Research). A second focus is the adsorption of fine dust by living and dead plant surfaces and the quantification of photosynthetic carbon gain by stem photosynthesis in woody plants and modelling their impact on climate change. As part of this work, Prof. Pfanz succeeded last year in publishing a much-discussed study in the field of bio-geomythology. The authors demonstrated in this study that the well-known mythological figure of the Cerberus, a three-headed dog guarding the entrance to the Underworld, is nothing other than deadly mofette gas. To verify this hypothesis the group conducted several studies in Turkey, Greece and Italy.

The group of Prof. Philipp Schmiemann (Empirical Teaching and Learning Research) investigates how school and university students can better understand biological subjects. The research focuses particularly on learning difficulties related to the interpretation of evolutionary phylogenetic trees and genetic family trees and on the conception of biological systems in ecology (food webs) and physiology (control loops). In a study with biology students from the USA and Germany, for instance, the research group investigated which situational factors affect learning success in the field of genetics. The knowledge gained from this study is now being used within the BMBF’s “Focus on Educational Justice” project to develop aca­demic teaching, among other things.