Press releases

FRANKFURT. Whether defective cells in the body will live or die is determined by a sophisticated control system. Death receptors play important roles in this system and translate information from outside the cell into critical cellular responses, which are often deregulated in diseases like cancer and inflammation. Cancer researcher Dr. Sjoerd van Wijk from Goethe University will investigate how these receptors function at the molecular level in a new research project which will receive €222,500 in funding over the next three years from the German Research Foundation (DFG). 

An effective regulation of programmed cell death is crucial for the correct development of embryos, a working innate immune system, and the prevention of cancer. How cells control the switch between cell survival and death, and which signalling pathways are involved, remain unclear. Proteins that interact with death receptors in these signalling pathways are often marked with various forms of ubiquitin chains, such as linear (M1) and K63-linked polyubiquitin chains. Deubiquitinating enzymes, which specifically break down ubiquitin chains, play a central role in the regulation of these chains, death receptor signalling, and cell fate.

“In our project, we want to investigate the network of M1-deubiquitinating enzymes and interactions with death receptor signalling in mammalian cells in order to understand the fundamental role of the ubiquitin in cell death or survival,” explains Sjoerd van Wijk, group leader at the Institute of Experimental Cancer Research in Pediatrics. The ultimate goal is to understand human diseases, in particular how cancer develops and spreads, and how cells protect themselves against invasive bacteria.

In his research group, van Wijk pursues multidisciplinary approaches using state-of-the-art technology. Through collaborations with Dr. Manuel Kaulich (CRISPR/Cas9 Screening Centre at Goethe University), he has access to highly efficient screening methods to unravel the molecular events that control death receptor function. The analysis of these molecular complexes is also being supported by the ubiquitin mass spectrometry at the Institute for Biochemistry II at Goethe University (Prof. Dr. Ivan Dikic) and at the Institute of Molecular Biology in Mainz (Dr. Petra Beli), as well as by the high-resolution microscopy at the Institute of Physical and Theoretical Chemistry at Goethe University (Prof. Dr. Mike Heilemann). 

An image may be downloaded at: http://www.uni-frankfurt.de/74652845
Credit: Dr. Sjoerd van Wijk

Further information: Dr. Sjoerd van Wijk, Institute for Experimental Cancer Research in Pediatrics, Faculty of Medicine, Niederrad Campus, Tel. +49 69 67866574, Email: s.wijk@kinderkrebsstiftung-frankfurt.de.

How does our nervous system motivate us to get off the sofa and walk to the fridge, or even to the supermarket, to get food? A research team led by Alexander Gottschalk from Goethe University investigated this using the threadworm Caenorhabditis elegans. The results indicate how foraging behaviour in higher animals might have evolved. 

Finding food and staying at a food source are crucial survival strategies in the animal world. But how are external feeding signals on the molecular, cellular and neuronal circuit level transformed into behaviour? To find out, neuroscientists often resort to less complex model species such as the nematode C. elegans. It only has 302 nerve cells and its network of connections has been precisely mapped, allowing scientists to investigate in detail how its nerve cells communicate with each other to achieve certain types of behaviour.   

Alexander Gottschalk and his team focused in this study on a neuronal circuit involving a pair of sensory nerve cells that detect the presence of food, and release the neuromodulator dopamine. This dopamine signal affects two types of downstream neurons, termed DVA and AVK and, as the team discovered, it does so in opposing ways. Dopamine activates DVA, promoting dwelling and local search behaviour, while inhibiting AVK, which promotes dispersal and long-range search behaviour. Specifically, this takes place by DVA and AVK signalling to further downstream motoneurons, which in turn control muscle activity. 

But what conclusions does this allow regarding foraging in higher animals such as humans? In the worm, the DVA neuron modulates locomotion by signalling to motoneurons via the neuropeptide NLP-12. Mammals have an equivalent to NLP-12, the neuropeptide cholecystokinin. Its release is also regulated by dopamine signalling, for example in reward-related behaviour like feeding. This shows that during evolution, the importance of dopamine and the neuropeptide cholecystokinin/NLP-12 as neuromodulators has been conserved. They influence motivated behaviour in the search for food intake, but also other actions, if rewarding sensations can be actively gained by certain behaviours. 

The neuron AVK, which acts as an antagonist to the DVA neuron, releases a neuropeptide called FLP-1 in the absence of food. FLP-1 acts as a counterpart to NLP-12/cholecystokinin in the worm. Although FLP-1 is more likely to be invertebrate-specific, similar 'RF-amide' neuropeptides are found in mammals, where they also control food intake. 

Thus, similar inhibitory balancing of cholecystokinin signalling may also be found in mammals. The C. elegans neuron types identified in this study may thus provide important guidance in the search for similar cell types in mammals where myriads of cells mediate similar mechanisms of motor control.

Publication 

Oranth et al.: Alexander Gottschalk et al.: Food sensation modulates locomotion by dopamine and neuropeptide signaling in a distributed neuronal network, in: Neuron 100, 1–15; December 19, 2018. (online November 1^st, 2018)

https://doi.org/10.1016/j.neuron.2018.10.024

You can download images here: http://www.uni-frankfurt.de/74664380

Image 1: The nematode C. elegans. Credit: Alexander Gottschalk, Goethe-Universität
Image 2: Nematode feeding tracks. Credit: A. Oranth
Image 3: Neuronal circuit controlling foraging behaviour by C. elegans. Creidt: A. Bergs, A. Gottschalk.

Further information:

Professor Alexander Gottschalk, Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Faculty 14, Max-von-Laue Strasse 15, Riedberg Campus, Tel.: +49 69 798 42518, a.gottschalk@em.uni-frankfurt.de

FRANKFURT. Once an SPD voter, always an SPD voter? This kind of consistency in voting behaviour is long gone. But what does the decreasing alignment of voters with political parties mean for parliamentary representation? Professor Thomas Zittel from Goethe University is looking into this questions together with an international team of researchers. The research group successfully won a grant from the German Research Foundation’s (DFG) Open Research Area (ORA) Programme.

The ORA project bears the title “The Nature of Political Representation in Times of Dealignment,” and examines the connection between citizens and parliament, which is essential for democracy. The last thirty years show a clear trend in this relationship: as mediating agent between citizen interests and parliamentary decision-making, political parties have lost the ability to provide linkage. How does this affect the way citizen interests are perceived and represented by parliamentary elites? While analyzing the behaviours of legislators in a mixed-methods approach, the international research team will investigate whether geographic and social ties between individual members of parliament and voters offer an alternative to, or an enhancement of, collective representation by political parties.

Zittel will closely collaborate with Prof. Rosie Campbell (King’s College London) and Prof. Tom Louwerse (Leiden University) in this project. The team will be funded for a period of two years and three months with a total of € 800,000. Zittel’s team is one out of 16 research teams that successfully applied for the fifth ORA Open Call (more than 300 pre-proposals were submitted in a two-stage process; 63 teams were invited to submit full proposals). ORA, which stands for Open Research Area, is run by the national research organizations of France (ANR), Germany (DFG), the Netherlands (NWO), and United Kingdom (ESRC).

Further information: Professor Thomas Zittel, Professor for Comparative Politics, Institute of Political Science, Faculty of Social Sciences, Westend Campus, Tel: +49 69 798-36678, E-Mail: zittel@soz.uni-frankfurt.de, Webseite: http://www.fb03.uni-frankfurt.de/42421522/tzittel

Further information on the fifth ORA Open Call: http://www.dfg.de/en/research_funding/announcements_proposals/2018/info_wissenschaft_18_66/index.html

FRANKFURT. Patients with rare diseases often go through a long history of suffering before finally receiving an accurate diagnosis. One reason for this is that the patient information necessary for research exists in varying languages and formats. This is set to change, thanks to a new European Joint Programme in which Goethe University plays an important role. 

For patients with rare diseases, the trek from doctor to doctor, and expert to expert, with a long paper trail of physician’s letters, test results, and images is practically a given. And when a diagnosis is finally made, they are faced with the difficulty of obtaining the correct therapy. To help these patients more quickly, valuable information regarding the course of the disease and its therapy, which is currently kept at individual healthcare institutions, must be made available for essential Europe-wide research. 

The European Joint Programme seeks to establish the technical and substantive requirements for clinical data to be used commonly for research purposes. Toward this end, Goethe University will receive the largest funding sum of all participating German institutions: more than one million euro over the coming five years. 

In Frankfurt, the focus will be on developing tools to integrate and standardise patient data. This includes software solutions for setting up disease-specific patient registries in which specific patient data can be collected on an ongoing basis. This will result in a representative patient group whose data can be analysed much more simply thanks to its standardization. 

“I think we can say with pride that in the future, Frankfurt will have a central role in Europe regarding the patient registry of rare diseases,” says Professor T.O.F. Wagner from the Frankfurt Reference Centre of Rare Diseases. Together with Dr. Holger Storf, Head of the Medical Informatics Group, he developed an open source registration platform for rare disease. The modules in it were used, among other things, to set up the European Rare Disease Registry Infrastructure. They also constitute the basis for the approved work in Frankfurt which, together with Professor Gernot Rohde, Head of Pneumonology at the University Hospital, should contribute to an improved interoperability of registries. 

“Rare diseases are a great example of a field of research that greatly profits from coordination at the European and international level, and which therefore requires technical support,” says Dr. Holger Storf. The new project should help overcome fragmentation and make cooperation easier. 

Within the EU project, already existing tools and programmes are to be consolidated and continued at a larger scale. Data from research, clinics, tests, processes, knowledge and know-how are to be shared throughout Europe in the future. In addition, an efficient model of financial support of all types of research on rare diseases – fundamental, clinical, health service – is to be introduced. The goal is an accelerated exploitation of research results in order to reduce the typical problems and ongoing suffering of patients.

Goethe University has already contributed to an improvement in the situation of patients with rare diseases through several different successful projects. In particular, the Mapping of Health Care Providers for People with Rare Diseases (www.se-atlas.de) deserves mention. It supports patients, their families, and health personnel in locating experts or patient organisations. The coordination and technical support of the European Reference Network for rare respiratory diseases (ERN-LUNG) is also in Frankfurt.

Further information:

Professor T.O.F. Wagner, Frankfurt Reference Centre for Rare Diseases, Faculty of Medicine, Niederrad Campus, Tel.: +49 (69)- 6301 87899, t.wagner@em.uni-frankfurt.de.

Dr. Holger Storf, Medical Informatics Group (MIG), University Hospital Frankfurt Frankfurt, Tel.: +49 (69) 6301-84438, storf@med.uni-frankfurt.de.

FRANKFURT. Robert Tampé, Director of the Institute of Biochemistry at Goethe University, has received € 1.5 million from the German Research Foundation (DFG) for a Reinhart Koselleck project. Through this programme, the DFG enables outstanding researchers to pursue exceptionally innovative, higher-risk projects. Tampé will address the functioning of the immune system in and on the surface of cells. 

“Our lives are repeatedly saved every day without us even knowing it,” states Robert Tampé. “Virtually undetected by us, our immune system constantly identifies and eliminates virus-infected cells, abnormal cells, and intra-cellular pathogens in an extremely efficient way. It’s a service provided by a well-functioning immune system.” Inversely, a malfunction or weakness in the immune system can lead to cancer, chronic illness and autoimmune diseases. 

It is known that infected cells trigger an immune reaction by attracting the attention of T-cells. They present protein fragments (antigens) from their cellular proteins on the cell surface. More specifically, the antigens are transferred to the so-called major histocompatibility complexes (MHC-I) and presented to the T-cells. Editing and loading complexes associated with the MHC-I play a key role in controlling the immune response. Still, these complexes have only been investigated to a very limited extent so far. 

“Viruses have developed sophisticated strategies to interfere with the antigen-loading of the MHC-I complexes and thus escape the attention of T-cells. In the Koselleck project, we want to elucidate some key mechanisms in the antigen processing,” says Tampé. The researcher expects that insights into the organization of these antigen quality control points will pave the way for a new understanding of intracellular multi-protein complexes associated with the cell membrane, and of chaperone complexes, which are important for the folding of proteins in the endoplasmic reticulum. In the long term, the findings should point to new therapy options for infections, autoimmune diseases, chronic illnesses and cancer. 

Robert Tampé is the Director of the Institute of Biochemistry and the Collaborative Research Center “Transport and Communication through Biological Membranes”, in which scientists from the Max Planck Institute of Biophysics team up with researchers of Goethe University Frankfurt. He is one of the founders of the Cluster of Excellence “Macromolecular Complexes” funded by the German Excellence Initiative. Before coming to Frankfurt, he was Director of the Institute of Physiological Chemistry at the Faculty of Medicine of the University of Marburg, and Research Group Leader at the Max Planck Institute of Biochemistry in Martinsried and the Technical University Munich. He worked with Harden M. McConnell at Stanford University as Max Kade Fellow. He is an Honorary Professor of Kyoto University and was recently appointed Visiting Fellow at Merton College and the Department of Biochemistry at Oxford University. 

As biochemist at the Biocenter in Frankfurt, Robert Tampé gained an international reputation for his fundamental contributions to the mechanistic understanding of antigen processing and to solving the question of how viruses avoid detection by the immune system. He also discovered the molecular machinery of ribosome recycling and provided structural and mechanistic insights into the quality control of protein biosynthesis. His main areas of interest include macromolecular complexes, membrane biology, as well as chemical and synthetic biology.

A picture may be downloaded at: www.uni-frankfurt.de/74506125

Credit: Goethe University/Uwe Dettmar

Further information: Prof. Dr. Robert Tampé, Institute of Biochemistry, Riedberg Campus, Tel. +49 69 798-29475, tampe@em.uni-frankfurt.de, http://www.biochem.uni-frankfurt.de/