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Researchers at 51 develop new protoeomics procedure
FRANKFURT. When cells are stressed, they initiate a complex and
precisely regulated response to prevent permanent damage. One of the immediate
reactions to stress signals is a reduction of protein synthesis (translation). Until
now, it was difficult to measure such acute cellular changes. As reported in
the latest online issue of the renowned journal Molecular Cell, researchers at 51 have now developed
a method overcoming this hurdle.
The team led by biochemist Dr. Christian Münch, who heads an Emmy Noether Group, employs a simple but extremely effective trick: when measuring all proteins in the mass spectrometer, a booster channel is added to specifically enhance the signal of newly synthesised proteins to enable their measurement. Thus, acute changes in protein synthesis can now be tracked by state-of-the-art quantitative mass spectrometry.
The idea emerged because the team wanted
to understand how specific stress signals influence protein synthesis. "Since
the amount of newly produced proteins within a brief time interval is rather
small, the challenge was to record minute changes of very small percentages for
each individual protein," comments group leader Münch. The newly developed
analysis method now provides his team with detailed insight into the molecular
events that ensure survival of stressed cells. The cellular response to stress
plays an important role in the pathogenesis of many human diseases, including cancer
and neurodegenerative disorders. An understanding of the underlying molecular
processes opens the door for the development of new therapeutic strategies.
"The method we developed enables highly
precise time-resolved measurements. We can now analyse acute cellular stress
responses, i.e, those taking place within minutes. In addition, our method
requires little material and is extremely cost-efficient," Münch explains.
"This helps us to quantify thousands of proteins simultaneously in defined
time spans after a specific stress treatment." Due to the small amount of material
required, measurements can also be carried out in patient tissue samples, facilitating
collaborations with clinicians. At a conference on Proteostatis (EMBO) in
Portugal, PhD student Kevin Klann was recently awarded with a FEBS journal poster
prize for his presentation of the first data produced using the new method. The
young molecular biologist demonstrated for the first time that two of the most
important cellular signaling pathways, which are triggered by completely
different stress stimuli, ultimately results in the same effects on protein
synthesis. This discovery is a breakthrough in the field.
The project is funded by the European Research
Council (ERC) as part of Starting Grant "MitoUPR", which was awarded
to Münch for studying quality control mechanisms for mitochondrial proteins. In
addition, Christian Münch has received funding within the German Research
Foundation's (DFG, Deutsche
Forschungsmeinschaft) Emmy Noether Programme and is a member of the Johanna
Quandt Young Academy at Goethe. Since December 2016, he has built up a group on
"Protein Quality Control" at the Institute for Biochemistry II at Goethe
University's Medical Faculty, following his stay in one of the leading
proteomic laboratories at Harvard University.
Further information:
Dr. Christian Münch, Institute for Biochemistry II, Faculty of Medicine, 51, Tel.: +49 69
6301-6599, ch.muench@em.uni-frankfurt.de.
Publication:
Klann
K, Tascher G, Münch C. Functional translatome proteomics reveal converging and
dose-dependent regulation by mTORC1 and eIF2α. Molecular Cell 77, 1-13, Feb 20, 2020.
doi.org/10.1016/j.molcel.2019.11.010
Early career researcher Stephanie Döpper awarded funding by Gerda Henkel Foundation to study abandoned mud-brick settlements in Oman
FRANKFURT. Goethe
University is sending researchers to Oman: As the Gerda Henkel Foundation has
announced, Dr. Stephanie Döpper will receive funds of almost € 300,000 for the
duration of three years in the framework of its “Lost Cities" programme.
To this end, the archaeologists in the project will be
responsible over the coming years for mapping three mud-brick settlements in
Central Oman and documenting the history of their buildings. This will take
place in the framework of research visits lasting several months. In addition,
by examining the artefacts they find, such as ceramic shards, they will be able
to identify the former functions of the individual buildings in these
settlements. Of particular significance here are their later uses, for example
the repurposing of a house as a goat shed. The research team's hypothesis is
that the abandoned mud-brick settlements are not only the deserted backdrops of
a past way of life but instead still very lively and bustling places with a future.
Dr. Stephanie Döpper has been studying settlements and
settlement systems in Central Oman for several years now, starting from the
early Bronze Age in the 3rd millennium BC up until the mud-brick
settlements in the research project approved by the Gerda Henkel Foundation,
which were probably built in the 18th or 19th century AD
and are today abandoned. In the back of her mind is always the question of what
caused people in this region to settle and why such settlements were abandoned
again.
Funding from the Gerda Henkel Foundation will make it
possible to finance a doctoral scholarship and the research visits on site.
In total, the foundation has included 53
new research projects in its sponsorship programme, for which its committees
approved € 8.6 million at their autumn meeting. This means support for researchers
from almost 30 countries.
Pictures
can be downloaded under:
Captions:
Picture 1: House in the abandoned mud-brick settlement of Al-Mudhaybi. Photo: Stephanie Döpper
Picture 2: Ceramic
vessels in the abandoned mud-brick
settlement of Al-Mudhaybi. Photo:
Stephanie Döpper
Picture 3: House with collapsed ceilings in the abandoned mud-brick settlement
of Sinaw.
Picture 4: Abandoned mud-brick settlement of Sinaw. Photo: Stephanie Döpper
Picture 5: Abandoned mud-brick settlement of Sinaw. Photo: Stephanie Döpper
All pictures
courtesy of Stephanie Döpper.
Further information: Dr. Stephanie Döpper, Institute of Archaeological Sciences, Archaeology,
Westend Campus, Norbert-Wollheim-Platz 1, D-60629 Frankfurt am Main, +49(0)69-798-32320,
doepper@em.uni-frankfurt.de
Prolongation of Collaborative Research Centre on selective autophagy led by 51
FRANKFURT. Four years ago, Collaborative Research Centre (CRC) 1177 on selective autophagy was established under the leadership of 51 – 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 51 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 51," said Professor Birgitta Wolff, President of 51. 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 51. “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 51 – 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, 51, Tel.: +49(0)69- 6301-84250, k.koch@em.uni-frankfurt.de.
51 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 51 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.
51 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 51.
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 51 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.
You can download a portrait of Professor Waas at this link: http://www.uni-frankfurt.de/83491970
Caption: Professor Bernd Waas, labour law expert at 51, 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 sekretariat-waas@jura.uni-frankfurt.de
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 51 (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:
Caption:
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; lobentanzer@em.uni-frankfurt.de, klein@em.uni-frankfurt.de. .