Prolongation of Collaborative Research Centre on selective autophagy led by Goethe University
FRANKFURT. Four years ago, Collaborative Research Centre (CRC) 1177 on selective autophagy was established under the leadership of Goethe University – now the German Research Foundation has given the green light for its further funding. A total of over € 12 million has been approved for the period up until 2023. Partners alongside Goethe University are the universities of Mainz, Munich, Tübingen and Freiburg, the Georg Speyer Haus and the Max Planck Institute of Biophysics in Frankfurt as well as the Institute of Molecular Biology (IMB) in Mainz.
Selective autophagy is part of the cell's waste disposal system. With its help, defective or potentially damaging cellular components are degraded and recycled. It plays a central role in maintaining cellular homeostasis and fulfils important functions in ageing and developmental processes. Errors in this system contribute to cancer, neurodegenerative disorders and infections. The objective of the research alliance is a better understanding of autophagy at molecular and cellular level in order to be able in future to counteract imbalances in the system. CRC 1177 is the first consortium in Germany to tackle this important topic systematically.
“This is very good news for Goethe University," said Professor Birgitta Wolff, President of Goethe University. Thanks to this CRC, Frankfurt has become a national hub for autophagy research over the past four years. Especially through the integration of new partners in Munich, Tübingen and Freiburg and at the MPI for Biophysics, it has been possible to substantially strengthen the existing partnership between Mainz (IMB/JGU) and Frankfurt (GSH/GU). We expect this research alliance to advance autophagy research significantly, which will help in the fight against many diseases," said the President.
Autophagy is found from simple organisms, such as yeasts, up to humans. The underlying molecular mechanisms are always similar: Cellular components that need to be removed are recognized in a highly specific manner, enveloped by membranes and degraded. This is how, for example, aggregated proteins are destroyed that would otherwise cause severe damage and trigger cell death. This can especially be observed in neurodegenerative disorders such as Alzheimer's disease, where toxic protein aggregates accumulate which then promote the massive destruction of nerve cells. Apart from proteins, autophagy can also target defective cell organelles and pathogens for removal. The cell can reutilize the recovered material as building blocks for synthesizing new components, which is why autophagy is also an important survival strategy in times of need.
Autophagy is a very complex process which must be precisely regulated and is greatly dependent on the cellular context. Its analysis requires state-of-the-art technologies, the integration of a wide variety of data and close collaboration between researchers from different disciplines. “We will focus on novel concepts in autophagy research and its impact on major biological processes as well as pathogenesis and therapy of human diseases," explains Professor Ivan Dikic, CRC spokesperson and Director of the Institute of Biochemistry II at Goethe University. “Our vision includes close interactions between basic and translational research via centrally supported technology platforms."
The platforms with their ultramodern equipment are a key factor in the research alliance's success: Since 2016, over 20 scientific publications have been produced in cooperation with the proteomics platform alone. In the second funding period, centrally available technologies will be significantly extended to include modelling and simulation methods, genomic and chemical high-throughput screening, and imaging methods to quantify autophagy in model organisms. Another equally important matter within the consortium is support for early career researchers. To this end, the Research Training Group set up in the first funding period will be continued. “Training the next generation of autophagy researchers is a matter close to our hearts and for this reason we've planned a diverse and advanced training programme," said Dikic.
Participating in the CRC on the part of Goethe University – in addition to its faculties of Biological Sciences, Biochemistry, Chemistry and Pharmacy, and Medicine – is the Buchmann Institute for Molecular Life Sciences.
Further information: Dr. Kerstin Koch, Institute of Biochemistry II, Faculty of Medicine, Goethe University, Tel.: +49(0)69- 6301-84250, firstname.lastname@example.org.
Goethe University is a participant in a project receiving 3.2 million Horizon 2020 grant
FRANKFURT. The European research project “Working, Yet Poor“ (WorkYP) was recently awarded 3.2 million euros for three years by the EU's Horizon 2020 programme. The project will investigate the social and legal reasons behind the increasing number of EU citizens who are at risk of living below the poverty line despite being employed. Law Professor Bernd Waas from Goethe University is heading a subproject.
“Countries implement certain measures to prevent in-work poverty, but there is not a set approach towards reducing or eliminating it. EU Member States – individually and collectively – need a better understanding of the problem, an understanding supported by pertinent data and which allows them to monitor and successfully attack it," says Luca Ratti, the WorkYP Project's coordinator and Associate Professor of European and Comparative Labour Law at the University of Luxembourg.
The distribution of in-work poverty differs substantially across Europe, due to different social and legal systems or measures implemented to reduce poverty. For example, 13.4% of the working population were at risk of poverty in Luxembourg in 2018, compared to 5.2% in Belgium. The reasons for such differences have not been sufficiently investigated. Therefore, the WorkYP Project will analyse seven representative countries with different social and legal systems (Luxembourg. Belgium, Germany, Italy, the Netherlands, Poland and Sweden) to document the problem and to propose best practice solutions to combat in-work poverty across all systems. “With this study, we intend to help EU Member States, and the EU as a whole, to better target their policies and regulatory action," Ratti explains.
The WorkYP Project has identified specific groups of people that are at greater risk of in-work poverty, on which the analysis will focus. These include low wage workers; self-employed people; those with temporary or flexible employment contracts; and casual or “zero-hours" workers. Because women are more frequently employed in low-paid jobs or are more vulnerable to unequal working conditions, the household's composition and income will be considered in the research.
Luca Ratti will lead a multinational and interdisciplinary research team comprised of researchers from eight European universities (Frankfurt, Bologna, Leuven, Rotterdam, Tilburg, Gdansk and Lund) as well as three social rights institutions active in Europe.
Goethe University will have a key role in this project. It will assume project leadership for the part of the project dedicated to consideration of employees with atypical work contracts. It will furthermore coordinate the work of the experts in the comparative analysis of the various models for combatting poverty at the workplace, and the system for guaranteeing a minimum living standard and a minimum catalogue of social rights. Overall, 320,000 euros in project funds will go to Goethe University. Professor Waas, who already heads the European Commission's labour law expert network, and also coordinates the project on the restatement of labour law in Europe, is pleased with his new task. “The days will be a bit longer, but it will be worth it," he says. “In particular with regard to the rapid digitalisation of the workplace and the emergence of completely new forms of work, numerous problems have come about that are in urgent need of answers."
“I am happy that Goethe University is involved in such an important European research project. Decent working and living conditions in all countries of the Community are of critical significance for Europe's future," says Professor Simone Fulda, who as Goethe University Vice President is in charge of research.
Horizon 2020, the EU Framework Programme for Research and Innovation launched in 2014, funds collaborative projects in research and innovation. Research organisations, universities, and companies are all eligible to participate. Horizon 2020 funds 6,000 projects each year and Luxembourg entities have already received approximately 40 million euros for more than 120 projects.
Caption: Professor Bernd Waas, labour law expert at Goethe University, heads the Frankfurt subproject of the Horizon 2020 collaborative project “Working, yet poor“.
Further information: Professor Bernd Waas, Chair for Labour Law and Civilian Law, Institute for Civil and Economic Law, Faculty of Law, Westend Campus, Phone+49 69-798 34232, E-Mail email@example.com
Sex-specific processes in schizophrenia and bipolar disorder
FRANKFURT. Recent studies have found a high genetic similarity of the psychiatric diseases schizophrenia and bipolar disorder, whose disease-specific changes in brain cells show an overlap of more than 70 percent. These changes affect gene expression, i.e., transcription of genes for the purpose of translation into functional proteins. A collaborative study carried out by the Institute of Pharmacology and Clinical Pharmacy at Goethe University (Professor Jochen Klein) and the Institute of Neurosciences at the Hebrew University of Jerusalem (Professor Hermona Soreq) now shows sex-specific biases in these changes, as well as in cellular control mechanisms based on endogenous short ribonucleic acid (RNA) chains.
The scientists identified an important role of microRNAs, a special group of these small RNA molecules, known for their extensive control of gene expression in all human cells. Targeting of a gene by one of these microRNAs can lead to a significant restriction of its expression. “The main problem is the enormous variety of possible combinations," says Sebastian Lobentanzer, lead author of the article published in the journal Cell Reports. “The human expresses about 2,500 of these microRNAs, and a single one can influence hundreds, maybe even thousands of genes."
For this reason, the researchers investigated gene expression in patient brains as well as human cultured nerve cells with a combination of RNA sequencing and bioinformatics. They found a difference in the expression of immune-related genes between men and women, especially with regard to cytokines, the messenger substances of immune cells. Upon exposition of the cultured male and female neuronal cells to some of these cytokines, the researchers found a transformation of nerve cells into to cholinergic neurons, defined by their use of the neurotransmitter “acetylcholine".
By sequencing the microRNAs at several time points during this process, the scientists were able to paint a detailed picture of the microRNA interface between the immune and neuronal systems. They identified the involvement of 17 partially sex-dependent families of microRNAs and generated an extensive network of 12,495 regulated genes. Using a multi-stage selection process, the most influential of these microRNA families were identified and confirmed in dedicated experiments. This led to the identification of the two sex-specifically expressed families mir-10 and mir-199 as interface between cytokines and cholinergic functions.
Psychiatric diseases are an important field for new therapeutic approaches because of their high genetic complexity and their inaccessibility to conventional forms of therapy. On the one hand, the current study demonstrates molecular parallels to the long-observed but previously unexplained clinical differences between disease-affected men and women. On the other hand, mechanisms on the basis of small RNA molecules could open up new avenues by influencing a large number of disease-relevant genes – a promising approach in the search for alternatives to traditional antipsychotic drugs. “Studies such as ours, which enable a comprehensive representation of microRNA interactions, are the first step on the path to developing new therapeutic substances," says Lobentanzer.
Publication: Lobentanzer S, Hanin G, Klein J & Soreq H (2019). Integrative Transcriptomics Reveals Sexually Dimorphic Control of the Cholinergic/Neurokine Interface in Schizophrenia and Bipolar Disorder. CellReports. ElsevierCompany. 1–19. doi: 10.1016/j.celrep.2019.09.017.
An image may be downloaded here: www.uni-frankfurt.de/83258617
The illustration shows a network of 212 microRNAs and their 12,495 targeted genes, deconstructed into four fields according to their sex-specific changes. (Copyright: Sebastian Lobentanzer)
Further information: Sebastian Lobentanzer, research scientist; Professor Jochen Klein; Institute for Pharmacology and Clinical Pharmacy, Riedberg Campus; firstname.lastname@example.org, email@example.com. https://slobentanzer.github.io/cholinergic-neurokine.
Scientists from Goethe University and Senckenberg Society for Nature Research are developing maps on the Zika virus infection risk
How the Zika virus can spread
Scientists from Goethe University and Senckenberg Society for Nature Research are developing maps on the Zika virus infection risk
FRANKFURT. The spread of infectious diseases such as Zika depends on many different factors. Environmental factors play a role, as do socioeconomic factors. Recently, several attempts have be made to predict the transmission risk of the Zika virus at a global and local level, but the spatial and temporal patterns of transmission are still not well understood. Researchers from Goethe University and the Senckenberg Society for Nature Research in Frankfurt were now able to generate reliable maps for the transmission risk of the Zika virus in South America.
The results have been published in the scientific journal “PeerJ". Based on the models for South America, they will use the method to determine the Zika risk for Europe as well. In most cases, mosquitoes of the genus Aedes transmit the Zika virus to humans. Primary vectors are the yellow fever mosquito (Aedes aegypti) and the Asian tiger mosquito (Aedes albopictus). Both mosquito species are widespread in South America. Whereas the yellow fever mosquito (Aedes albopictus) is nearly absent in Europe, the Asian tiger mosquito is widespread in the Mediterranean region.
“With our new modelling approaches we can illustrate the risk areas for Zika infections in Latin America," says Sven Klimpel Professor for Parasitology and Infection Biology at Goethe University in Frankfurt and the Senckenberg Biodiversity and Climate Research Centre. “The models additionally allow us to illustrate Zika risk areas for Europe. For example, our models indicate the two autochthonous cases in southern France in Département Var (see illustration)." At the end of October, French authorities announced the first Zika case in Europe; about a week later, a second case was made public.
According to the researcher's calculations, the Zika infection risk in South America is highest along the Brazilian East Coast and in Central America. The risk is moderate in the Amazon region and lowest in the southern areas of the continent. The following countries are especially affected according to the model: Brazil, Columbia, Cuba, the Dominican Republic, El Salvador, Guatemala, Haiti, Honduras, Jamaica, Mexico, Puerto Rico and Venezuela. In Europe, a risk of infection exists mainly in the Mediterranean region, but also in the inland regions of France and in the Rhine areas of Baden-Württemberg.
To determine the infection risk of a specific area, the researchers Dr Sarah Cunze and Professor Sven Klimpel modelled the potential spread of the two species of mosquito, Aedes aegypti and Aedes albopictus. Since the mosquitoes can only transmit the Zika virus in regions where the virus is present in the first place, the researchers included an Evidence Consensus Map in their risk model. This map categorises the number of reported Zika illnesses at the regional level. The average temperature of the warmest quarter was also incorporated in the model, since temperature has a significant influence on whether the virus can survive and multiply in the mosquito. Finally, the scientists added socioeconomic factors such as population density and gross domestic product to their risk model
Publication: Cunze S, Kochmann J, Koch LK, Genthner E, Klimpel S. 2019. Vector distribution and transmission risk of the Zika virus in South and Central America. PeerJ 7:e7920 DOI 10.7717/peerj.7920
An image maybe downloaded here: http://www.uni-frankfurt.de/83225123
Illustration 1: Correlative modelling approach for regions with increased Zika infection risk in South America. In addition to the modelled expansion of the two main vector types (Aedes aegypti a1 and Ae. albopictus a2), the model incorporates the average temperature of the warmest quarter (b), the occurrence of the Zika virus (c) and the Dengue virus (e), population density (f) and the gross domestic product.
Illustration 2: Zika infection risk modelled for South America.
Illustration 3: Regions where an autochthonous transmission of the Zika virus through the bite of an infected tiger mosquito is possible, since the temperature conditions are suitable (red areas) and the tiger mosquito is already present as vector species (hatched areas).
Further information: Professor Sven Klimpel, Institute for Ecology, Evolution and Diversity, Faculty 15 (Biosciences), Riedberg Campus, phone +49 69 798-42237, E-Mail firstname.lastname@example.org
Study at Goethe University shows: ECB communication strongly affects financial markets
FRANKFURT. Eight times a year, the European Central Bank (ECB) sets the key interest rate and announces it through press releases and press conferences. A study by Professor Christian Wagner (Vienna University of Economics and Business) and Professor Maik Schmeling (Goethe University Frankfurt) shows that not only the key interest rate but also the way the ECB communicates it has an impact on financial markets.
The ECB's most important job is to ensure price stability in the euro area, avoiding major fluctuations in the value of money and maintaining an inflation rate of around 2%. One important instrument for this is the key interest rate, which forms the basis both for financial market transactions and for the conditions applied to savings and loans. If the ECB lowers the key interest rate, saving money become less attractive, while loans become more affordable. Approximately every six weeks, the ECB sets the current key interest rate and publishes its decision at 1:45 pm in a short announcement. At 2:15 pm this is followed by a press conference in which the central bank explains the rationale behind its interest rate decision and gives its assessment of further economic developments.
In a current research project, Christian Wagner (Vienna University of Economics and Business) and Maik Schmeling from Goethe University investigated whether the way in which the ECB communicates it monetary policies is also reflected in asset prices such as stocks. The result: a change in the ECB's tone has a significant effect on the prices of financial instruments. If the ECB's word choice is more positive, then stock prices rise, while derivatives used to hedge risks become cheaper. “A positive word choice seems to increase market participants' willingness to take risks, leading to rising stock prices," says Maik Schmeling from Goethe University. The authors were also able to show that a more optimistic tone on the part of the ECB is an indicator of more favourable economic developments. Future interest rate changes can be predicted based on the tone of the ECB's communications. In other words, the way in which the ECB communicates with the market allows conclusions to be drawn about its future interest rate policy.
The results of this study are particularly relevant with regard to central banks' capacity to act, because they show that through their choice of words, central banks can influence market participants' expectations and willingness to take risks. The communication strategy of a central bank therefore represents an instrument of money policy on its own. For market participants, the results of the study mean that listening closely to the tone of the ECB will provide additional clues for making investment and financing decisions. The authors of the study analysed the ECB's tone and generated a time series of changes in tone from one press conference to the next. This makes it possible to observe how stock prices and other financial instruments changed depending on the ECB's tone. For their analysis, Wagner and Schmeling used high-frequency financial data, which is available at one-minute intervals, allowing them to track price developments right from the start of the press conference. In their analysis, the researchers also controlled for the level of interest rate changes and other “hard facts" published during the press conference, such as growth and inflation forecasts.
Maik Schmeling has been professor for finance at the Faculty of Business and Economics at Goethe University since May 2018. From 2013 to 2018, he was professor of finance at the Cass Business School, City, University of London. In his research, Maik Schmeling focuses on various issues in the field of international financial markets, such as risk premiums on currency and money markets, the connection between monetary policies and asset prices, and the formation of expectations on financial markets. Schmeling has published in such internationally renowned publications as the “Journal of Finance," the “Journal of Financial Economics" and the “Review of Financial Studies."
Publication: Schmeling, Maik and Wagner, Christian, Does Central Bank Tone Move Asset Prices? (October 23, 2019). Available at: https://ssrn.com/abstract=2629978 or http://dx.doi.org/10.2139/ssrn.2629978
Further information: Maik Schmeling, Professor für Finance, Finances Department, Faculty of Business and Economics, Westend Campus, email@example.com