Whether it is new and groundbreaking research results, university topics or events – in our press releases you can find everything you need to know about the happenings at Goethe University. To subscribe, just send an email to firstname.lastname@example.org
Fundamental structural difference to earlier models
FRANKFURT.Elongated fibres (fibrils) of the beta-amyloid protein form the typical senile plaques present in the brains of patients with Alzheimer's disease. A European research team and a team from the United States (Massachussetts Institute of Technology in cooperation with Lund University) have simultaneously succeeded in elucidating the structure of the most disease-relevant beta-amyloid peptide 1–42 fibrils at atomic resolution. This simplifies the targeted search for drugs to treat Alzheimer's dementia.
Alzheimer's disease is responsible for at least 60 percent of dementia cases worldwide. It causes enormous human suffering and high costs. A cure or causal therapy are not yet available. A reason for this is that the exact course of the illness in the brain at a molecular level has not yet been adequately clarified.
It is known that the beta-amyloid peptide plays a crucial role. This peptide, 39 to 42 amino acids long, is toxic to nerve cells and is able to form elongated fibrils. Beta-amyloid peptide 1–42 and beta-amyloid peptide 1-40 are the two main forms that appear in senile plaques. We do not know why these lead to the decay of nerve cells in the brain, but this question is very interesting for the development of medications to treat Alzheimer's disease.
In a joint project between the Swiss Federal Institute of Technology in Zurich, the University of Lyon, and the Goethe University in Frankfurt am Main, in cooperation with colleagues at the University of Irvine and the Brookhaven National Laboratory, researchers have succeeded in determining the structure of a beta-amyloid peptide 1–42 fibril at an atomic resolution. This fibril presents the greatest danger in this disease. The researchers built on earlier research on the structure of beta-amyloid monomers done at the University of Chicago. Further immunological examinations show that the investigated form of the fibrils is especially relevant to the illness.
Protein fibrils are visible in electron microscope images (Fig. 1), but it is very difficult to go to an atomic level of detail. The standard methods used in structural biology to achieve this assume that the macromolecule is present as a single crystal or in the form of individual molecules that are dissolved in water. However, fibrils are elongated structures that adhere to each other and neither form crystals, nor can be dissolved in water.
Only solid-state nuclear magnetic resonance spectroscopy (solid-state NMR) is capable of offering a view at the atomic level in this case. New developments in methods made it possible to measure a network of distances between the atoms in the protein molecules that make up a fibril (Fig. 2). Extensive calculations enabled the atomic structure of the fibril to be reconstructed from these measurements.
The main part of the beta-amyloid 1-42 peptide is shaped like a double horseshoe (Fig. 3). Pairs of identical molecules form layers, which are stacked onto each other to form a long fibril. Numerous hydrogen bonds parallel to the long axis lend the fibrils their high stability.
"The structure differs fundamentally from earlier model studies, for which barely any experimental measurement data was available." explains Prof Peter Güntert, professor of computational structural biology at Goethe University.
The publications released by the two teams, which confirm each other, have caused excitement in expert circles, as they enable a targeted, structure-based search for medicines that will attack the beta-amyloid fibrils. The researchers hope that this scourge of old age, first described 110 years ago by the Frankfurt-based physician Alois Alzheimer, will finally be defeated over the next one or two decades.
Wälti, M. A., Ravotti, F., Arai, H., Glabe, C., Wall, J., Böckmann, A., Güntert, P., Meier, B. H. & Riek, R. Atomic-resolution structure of a disease-relevant Aβ(1-42) amyloid fibril. Proceedings of the National Academy of Sciences of the United States of America, DOI 10.1073/pnas.1600749113.
Colvin, M. T., Silvers, R., Ni, Q. Z., Can, T. V., Sergeyev, I., Rosay, M., Donovan, K. J., Michael, B., Wall, J., Linse, S. & Griffin, R. G. Atomic resolution structure of monomorphic Aβ42 amyloid fibrils. Journal of the American Chemical Society, DOI 10.1021/jacs.6b05129.
Xiao, Y., Ma, B., McElheny, D., Parthasarathy, S., Long, F., Hoshi, M., Nussinov, R. & Ishii, Y. Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer’s disease. Nature Structural & Molecular Biology 22, 499–505 (2015).
Images are available for download here: www.uni-frankfurt.de/62697618
Fig. 1: Electron microscope image of Alzheimer fibrils
Fig. 2: Network of distance measurements in the protein molecule
Fig. 3: Structure of the amyloid-beta 1–42 fibrils
Information: Prof. Peter Güntert, Institut of Biophysical Chemistry, Campus Riedberg, Tel.: (069)-798-29621, email@example.com.
Telling smells from the latrine
FRANKFURT. What are the neighbours up to? The European rabbit (Oryctolagus cuniculus) can tell from the smell of their latrines, which mark the boundary of their territory like a fence. Latrines located near their own burrow, on the other hand, serve to exchange information within the group. As a group of researchers at Goethe University has now discovered, urban rabbits use the latrines along the territorial boundary more often and thus display a greater need to segregate themselves from their neighbours.
Rabbits communicate with each other via scents in their urine or faeces. By snuffling at the latrine, they learn everything there is to know about the age, gender or social status of the other users. Urban rabbits, however, demonstrate a completely different behaviour to that of their rural brethren when using the latrines, as Madlen Ziege, doctoral researcher in the Ecology and Evolution Working Group at Goethe University reports in the current issue of the “BMC Ecology” online journal.
Whilst wild rabbits in the countryside deposit more latrines in close proximity to their burrows and also use these more often, their relatives in the city behave quite differently. Along the rural-to-urban gradient, researchers not only found a particularly large number of latrines along territorial boundaries, i.e. quite a distance away from the burrow, but also signs that these were used more frequently than those right next to the burrow. “The depositing of latrines as a means of communication between neighbouring social groups in order, for example, to demarcate territory, is therefore particularly significant amongst wild rabbits in Frankfurt’s inner city,” explains Madlen Ziege.
Findings from earlier studies deliver a good explanation for these observations: In the centre of Frankfurt only a few wild rabbits – often even just one or a pair – live in a burrow. However, burrow and rabbit population densities are very high here and thus also the competition for resources. Clear segregation from the neighbours seems to be of particular importance here, whilst “internal” communication in a group which is anyhow small is less important. In the countryside surrounding Frankfurt, by contrast, large social groups inhabit extensive burrow systems; burrow and rabbit population densities are comparatively low here. Communication within the same social group is consequently of greater importance.
Publication: Ziege M, Bierbach D, Bischoff S, Brandt A–L, Brix M, Greshake B, Merker S, Wenninger S, Wronski T, Plath M (2016) Importance of latrine communication in European rabbits shifts along a rural–to–urban gradient. BMC Ecology, http://bmcecol.biomedcentral.com/articles/10.1186/s12898-016-0083-y
Information: Madlen Ziege, Ecology and Evolution Working Group, Riedberg Campus, Tel.: 0157 73883101, firstname.lastname@example.org
Cylinder-shaped structures measure saturated and unsaturated fatty acids
FRANKFURT.Not only humans but also each of their body cells must watch their fat balance. Fats perform highly specialised functions, especially in the cell membrane. A research group at the Buchmann Institute for Molecular Life Sciences (BMLS) of Goethe University in Frankfurt, together with colleagues at the Max Planck Institute of Biophysics, has now discovered how yeast cells measure the availability of saturated and unsaturated fatty acids in foodstuffs and adapt their production of membrane lipids to it. This opens up new possibilities to understand the production and distribution of fatty acids and cholesterol in our body cells and make them controllable in future, report the researchers in the latest issue of the “Molecular Cell” journal.
A glance in the supermarket refrigerator shows: Low fat, less fat and no fat are en vogue. Yet fats are essential for cell survival as they form the basic structure for the biological membranes which separate cells from the environment and form functional units inside them. In this way, opposing reactions, such as the formation of energy stores and consumption of fat, can be organised in one and the same cell.
“Membrane lipids have a large number of vital cellular functions. They impact on signal transmission from cell to cell, but also affect intracellular communication,” explains Professor Robert Ernst, whose research group at the BMLS has been on the trail of fats’ hidden functions for years. “Hormone-producing cells are particularly susceptible to perturbed fatty acid metabolism and often have difficulties in regulating their membrane lipid composition. A malfunction of fatty acid regulation can, however, lead to cell death and – depending on the type of cell – trigger diseases such as diabetes.”
First observations that living organisms such as bacteria can actively control their fatty acid production were already made decades ago. Yet until recently researchers puzzled over how higher organisms, for example fungi such as baker’s yeast, measure and regulate the ratio of saturated and unsaturated fatty acids in their membrane lipids. Thanks to funding from the German Research Foundation and the Max Planck Society, the working groups headed by Robert Ernst at Goethe University Frankfurt and Gerhard Hummer at the Max Planck Institute of Biophysics have been able to investigate this fundamentally important question.
In order to describe the mechanism of a membrane sensor which measures the degree of lipid saturation in the yeast cell, the researchers used genetic and biochemical methods and simulated the motions and underlying forces of membrane lipids over a period of a few milliseconds by means of extensive molecular dynamic simulations.
These efforts revealed that the sensing mechanism is based on two cylinder-shaped structures which are positioned next to each other in biological membranes. They both exhibit a rough and a smooth surface respectively and rotate around each other. “It’s like a finger in cookie dough that checks how much butter has been added,” explains Robert Ernst. As saturated fats cannot be accommodated by the rough surface of the helix while unsaturated fats can, the fat sensor’s structure changes depending on the membrane environments. Intriguingly, this conformational change can control the downstream production of unsaturated fatty acids.
“This finding paves the way for many more studies”, predicts Robert Ernst. “With our knowledge of this delicate mechanism in yeast we can now focus on finding new sensors in different organelles and species which monitor and control the production of unsaturated fatty acids and cholesterol in our body.” In view of the far-reaching potential of these findings, an international conference will be staged in the near future. The organisers, including researchers from Frankfurt, expect that many cellular functions of membrane lipids will be revisited from a new perspective and that it will be possible to support hormone-producing cells in a more targeted manner.
Roberto Covino, Stephanie Ballweg, Claudius Stordeur, Jonas B. Michaelis, Kristina Puth, Florian Wernig, Amir Bahrami, Andreas M. Ernst, Gerhard Hummer, and Robert Ernst: A Eukaryotic Sensor for Membrane Lipid Saturation, Molecular Cell (2016), http://dx.doi.org/10.1016/j.molcel.2016.05.015
A video of the dancing fat sensors can be found under:
Further information: Prof. Robert Ernst, Buchmann Institute for Molecular Life Sciences, Riedberg Campus, Tel.: (069) 798-42524,email@example.com.
Exceptional dissertations on intellectual and industrial property law and financial market supervision in the U.S.
Law students Anja Becker and Jenny Gesley have received the 2015 Baker & McKenzie Award for the best dissertations in commercial law at Goethe University in Frankfurt. The two winners received the award during the doctoral awards ceremony at the law department. The Award, which has been given to the authors of exceptional dissertations and professorial theses in the area of commercial law every year since 1988, is given alongside a monetary prize of EUR 6,000.
Anja Becker convinced the jury with her dissertation on "Coordination of proceedings in transnational intellectual and industrial property law disputes" (Verfahrenskoordination bei transnationalen Immaterialgüterrechtsstreitigkeiten). Intellectual and industrial property law is about "intellectual property", which includes patent law, copyright law and trademark law. The awardee examined the question of how parallel, yet related, proceedings can be coordinated, a topic of relevance where intellectual and industrial property law and international private and civil proceedings law intersect. "On the whole, Anja presented a thesis displaying top-notch reasoning on all levels of scientific legal work. This applies to the interpretation of the Brussels Ibis Regulation, the systematization of different case groups from a comparative perspective and last but not least, the prospect of future improvements in the coordination of transnational intellectual and industrial property law disputes", says Prof. Dr. Alexander Peukert, the Chair for Civil Law and Commercial Law at Goethe University and academic supervisor of the award-winning thesis.
Jenny Gesley's thesis "Financial markets supervision in the U.S. National developments and international standards" (Die Aufsicht über die Finanzmärkte in den USA. Nationale Entwicklungen und internationale Vorgaben) conveys a clear and concise impression of the efforts made by U.S. Americans to avert hazards originating from the financial markets with the help of legal measures, says Prof. Dr. Dr. h.c. Helmut Siekmann, academic supervisor of this thesis. He is Deputy Managing Director of the Institute for Monetary and Financial Stability (IMFS) of the House of Finance and holder of the Endowed Chair of Money,Currency and Central Bank Law at Goethe University. He referred to the thesis as an "impressive accomplishment", stating that, "it is in fact partially on a par with a professorial thesis". By consistently pursuing her chosen approach based on historical development, Jenny Gesley had successfully managed to present comprehensive findings for financial markets as a whole.
All dissertations that focus on aspects of commercial law and have been granted "summa cum laude" honors are taken into consideration for the Baker & McKenzie Award each year, as well as professorial theses on aspects of commercial law that were written within an academic year. "By sponsoring the award, we emphasize our close ties with Goethe University and how important the promotion of young legal talent is to our law firm," says Dr. Christian Reichel, member of the management team of Baker & McKenzie Germany and Austria who will hand over the award to the two winners. The law firm has been sponsoring students of Goethe University in the National Scholarship Program from its creation, and Baker & McKenzie attorneys have a long tradition of teaching there.
The crucial step takes place in the dark
FRANKFURT. Birds have a light-dependent compass in their eyes. This compass gives them information about the direction of the Earth's magnetic field. Prof. Roswitha Wiltschko's research groupat Goethe University Frankfurt, together with French colleagues, has elucidated how this compass works at the molecular level.
Birds have two sensory organs for orientation and navigation in the Earth's magnetic field: They use their beak to measure the strength of the magnetic field, while their eyes provide directional information. One type of cone photoreceptors in the birds' eyes is sensitive to UV light and also contains a form of the protein cryptochrome. Previous studies of the Frankfurt researchers suggested that most likely it is this protein that enables birds to detect the magnetic field.
A cyclic reaction involving one light-dependent and one light-independent step takes place in the cryptochrome. Two radical pairs are formed during this cycle, and their unpaired valence electrons react to magnetic fields. The Frankfurt group, working in collaboration with Pierre and Marie Curie University Paris, have now discovered which of these two radical pairs is crucial for navigation in the Earth's magnetic field.
In a behavioural study on robins, the birds were subjected to two experimental conditions: (1) at one-second intervals, the researchers switched off either the light or the Earth's magnetic field while keeping the other stimulus constant; (2) the stimuli alternated in one-second intervals, such that light and magnetic field were not present at the same time. Even in the latter condition the birds could still orient along the Earth's magnetic field lines. The group concludes that the light-independent radical pair is responsible for detecting the magnetic field lines. Light is only required to keep the cycle going.
"This is the first proof that the radical pair generated in darkness is the crucial one for the magnetic compass", says Prof. Roswitha Wiltschko. Since in other organisms cryptochrome is used exclusively for the perception of light, the study indicates that there has been a special evolutionary adaptation in birds.
Information: Prof. Roswitha Wiltschko & Christine Nießner, Institute for Ecology and Diversity, Prof. Wolfgang Wiltschko, Institute for Cell Biology and Neuro Sciences; Phone +49(0)69 798-42119 or +49(0)6032 81206; firstname.lastname@example.org; email@example.com.
Publication: Wiltschko R, Ahmad M, Nießner C, Gehring D, Wiltschko W. 2016 Light-dependent magnetoreception in birds: the crucial step occurs in the dark.J. R. Soc. Interface 20151010.