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Single-molecule microscopy visualises the dance of receptors
FRANKFURT. Whether
a sick cell dies, divides, or travels through the body is regulated by a
sophisticated interplay of signal molecules and receptors on the cell membrane.
One of the most important molecular cues in the immune system is Tumour Necrosis
Factor α (TNFα). Now, for the first time, researchers
from Goethe University have visualised the molecular organisation of individual
TNFα receptor molecules and the binding of TNFα to the cell membrane in cells
using optical microscopy.
Before
TNFα can bind to a membrane receptor, the TNFR receptor must first be activated.
By doing so, the key will only fit the lock under certain circumstances and prevents,
among other things, that a healthy cell dies from programmed cell death. “For
TNFR1 in the membrane, the binding of TNFα is mediated through several cysteine-rich
domains, or CRDs," explains Sjoerd van Wijk form the Institute for Experimental
Cancer Research in Paediatrics and the Frankfurt Stiftung für Krebskranke
Kinder at Goethe University.
In particular, CRD1 of the TNFR1 makes it
possible for TNFα to “attach". Researchers already knew that TNFR1 molecules cluster
in a fashion similar to a dance, in which two, three or more partners grasp
hands – with the dimers, trimers or oligomers consisting of single TNFR1 molecules
– in the case of TNFR1. This kind of “structural reorganization" also takes
place when there is no TNFα present. “Despite the significance of TNFα for many
diseases, including inflammation and cancer, the physiology and patterns of TNFR1
in the cell membrane still remain largely unknown up to now," says Sjoerd Van
Wijk, explaining the starting point for his research.
In order to understand the processes in the cell
membrane in detail, van Wijk approached Mike Heilemann from the Institute for
Physical and Theoretical Chemistry at Goethe University. Using a combination of
quantitative microscopy and single-molecule super-resolution microscopy that he
developed, Heilemann can visualise individual protein complexes as well as their
molecular organisation in cells. Together with Ivan Dikic (Institute for
Biochemistry II) and Simone Fulda (Institute for Experimental Cancer Research
in Paediatrics) from Goethe University, Harald Wajant from the University
Hospital Würzburg and Darius Widera from University Reading/UK, they were able to
observe the dance of the TNFα receptors. Financial support was provided by the
Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research Centre
807 “Transport and Communication across Biological Membranes".
As the researchers report in the current issue of
“Science Signalling", membrane TNFR1 receptors exist as monomers and dimers in
the absence of TNFα. However, as soon as TNFα binds TNFR1, receptor trimers and oligomers are formed
in the membrane. The researchers also found indications for mechanisms that
determine cell fate independently of TNFα. These findings could be relevant for
cancer or and inflammatory diseases such as rheumatoid arthritis. “It clearly
opens new paths for developing novel therapeutic approaches," states van Wijk.
Publication: C. Karathanasis, J. Medler, F. Fricke, S. Smith, S.
Malkusch, D. Widera, S. Fulda, H. Wajant, S. J. L. van Wijk, I. Dikic, M.
Heilemann, Single-molecule imaging reveals the oligomeric state of functional
TNFα-induced
plasma membrane TNFR1 clusters in cells. Sci. Signal. 13, eaax5647 (2020). DOI: 10.1126/scisignal.aax5647
Further
information: Dr Sjoerd van Wijk, Institute for
Experimental Cancer Research in Paediatrics, Niederrad Campus, Tel.: +49 69 67866574, Email: s.wijk@kinderkrebsstiftung-frankfurt.de
Prof Mike Heilemann, Institute for Physical and Theoretical
Chemistry, Riedberg Campus, Tel.: +49 69 798 29424, Email: heileman@chemie.uni-frankfurt.de
In ruminants, a bacterium reacts to fluctuating sodium content with two different respiratory circuits
FRANKFURT. Cows can adapt themselves to a fluctuating sodium
content in their feed. How they do that was so far a secret. Researchers from
Goethe University have now discovered a bacterium in the microbiome of the
rumen which has a new type of cell respiration.
The cow can only process grass in its rumen with the
help of billions of microorganisms. An entire zoo of bacteria, archaea and
protozoa works there like on a production line: First of all, these single-cell
organisms break down the cellulose, a polysaccharide. Other bacteria ferment
the sugars released into fatty acids, alcohols and gases, such as hydrogen and
carbon dioxide. Finally, methanogenic archaea transform these two gases into
methane.
An average cow
produces about 110 liters of methane per day. It escapes from its mouth through
rumination, but also mixes again with partly digested food. As a result, the sodium
content of the grass pulp can fluctuate to a considerable degree (between 60
and 800 millimoles of sodium chloride (NaCLl) per liter).
A
German-American research team has now discovered how the ruminal bacteria adapt
to these extreme fluctuations in sodium content: “Bioinformatic analyses of the
genome of ruminal bacteria led our American colleague Tim Hackmann to assume
that some ruminal bacteria have two different respiratory circuits. One of them
functions with sodium ions and the other without," explains Professor Volker
Müller from the Department of Molecular Microbiology and Bioenergetics at
Goethe University. That is why Müller suggested to his doctoral researcher
Marie Schölmerich that she study a typical representative in the microbiome of
ruminants: the bacterium Pseudobutyrivibrio
ruminis.
Together with
undergraduate student Judith Dönig and Master's student Alexander Katsyv, Marie
Schölmerich cultivated the bacterium. Indeed, they were able to corroborate both
respiratory circuits. As the researchers report in the current issue of the Proceedings
of the National Academy of Sciences (PNAS), the electron carrier ferredoxin
(Fd) is reduced during sugar oxidation. Reduced ferredoxin drives both respiratory
circuits.
The one
respiratory circuit comprises the enzyme complex Fd:NAD oxidoreductase (Rnf complex). It
uses energy to transport sodium ions out of the cell. When they re-enter the
cell, the sodium ions trigger an ATP synthase, so that ATP is produced. This
respiratory circuit only works in the presence of sodium ions.
In the absence of sodium ions, the bacterium forms an alternative respiratory
circuit with another enzyme complex: The Ech hydrogenase (synonymous: Fd:H+ oxidoreductase)
produces hydrogen and pumps protons out of the cell. If these re-enter the cell
via a second ATP synthase that accepts protons but not sodium ions, ATP is also
produced.
“This is the first
bacterium so far in which these two simple, completely different respiratory
circuits have been corroborated, but our bioinformatic analyses suggest that
they are also found in other bacteria," explains Marie
Schölmerich. “It seems, therefore, that this adaptation strategy is more
widespread," she assumes.
Interestingly, both enzyme complexes (Rnf and Ech) were also discovered in bacteria which are old in terms of evolutionary biology. Professor Müller's research group has examined them in depth, but always only found one of the two enzyme complexes and never both together. “We're now going to use synthetic microbiology methods to produce hybrids of bacteria that contain both complexes in order to optimize them for biotechnological processes. In this way, we can raise the cellular ATP content, which will make it possible to produce products of a higher quality," explains Professor Müller. The intention is to use the respiratory circuits to recover valuable substances through the fermentation of synthesis gas. This is the subject of the trials being conducted in the framework of a project sponsored by the Federal Ministry of Education and Research.
A picture can be downloaded under: https://www.muk.uni-frankfurt.de/84412971?
Caption: The bacterium
Pseudobutyrivibrio ruminis (green), a
typical ruminal bacterium, obtains energy via two different respiratory
circuits. The one requires sodium ions, the other hydrogen ions (H+). In this way, it
can adapt to fluctuating sodium concentrations in animal feed in an optimum way.
Picture: Goethe University/ Cow: Shutterstock
Publication: Schölmerich,
M.C., Katsyv, A., Dönig, J., Hackmann, T., Müller, V. (20XX). Energy
conservation involving two respiratory circuits. Proc. Natl. Acad. Sci. U.S.A.,
in press.
Further information: Professor
Volker Müller, Molecular Microbiology and Bioenergetics, Riedberg Campus, Tel.:
+49(0)69-798-29507; VMueller@bio.uni-frankfurt.de.
With the Centre for Biomolecular Magnetic Resonance, Goethe University is one of 23 European partners in the project iNEXT-Discovery
FRANKFURT. Determining the structure of large biomolecules is
critical to many innovations in the fields of health, environment and
sustainable technologies. Because structural research requires expensive
equipment such as NMR spectrometers, the European Union funds research
infrastructure. Beginning in February 2020, an additional € 10 million will be
invested in the project iNEXT Discovery. The Centre for Biomolecular Magnetic
Resonance (BMRZ) at Goethe University is a part of the project once again.
Currently, the iNEXT Collaboration is made up of 23 partners from 14 European countries. It is the first research infrastructure project combining different structural biological methods: X-ray spectroscopy, nuclear magnetic resonance spectroscopy (NMR), electron microscopy and biophysical methods. These methods make it possible to decode the three-dimensional structure of biological macromolecules in order to understand their function within the complex machinery of life. The goal is to develop new medicines, improved vaccinations, new biomaterials, biofuels, and enzymes for food production.
BMRZ at Goethe
University makes its expertise in NMR spectroscopy available to researchers
throughout Europe. Visitors from other countries already use the equipment
daily to determine the structures of proteins, RNA and DNA. It is furthermore
possible for industrial partners to participate via cooperation contracts in
order, for example, to search specifically for active substances. Training
programmes will be set up in the next four years for researchers with little
previous experience with NMR.
“At BMRZ, we
give European scientists access to the currently most powerful NMR
technologies. In the next funding period, a 1.2 gigahertz NMR spectrometer will
be available," says Professor Harald Schwalbe, Board Member of iNEXT-Discovery.
“From 2020 onwards, we expect that 20 user groups annually will come from all
over Europe to use our equipment and profit from our experience. In this way,
we are all contributing to exciting science."
Further
information: Professor Harald Schwalbe, BMRZ, Institute for Organic Chemistry and Chemical
Biology, Tel.: +49-69-798-29737; Email: schwalbe@nmr.uni-frankfurt.de
Dr Tobias Freimüller receives the Rosl and Paul Arnsberg Prize from the Polytechnic Foundation of Frankfurt am Main
FRANKFURT. Dr
Tobias Freimüller, Deputy Director of the Fritz Bauer Institute at Goethe
University has been awarded the 2019 Rosl and Paul Arnsberg Prize from the
Polytechnic Foundation of Frankfurt am Main. The award, which is given every
three years, recognizes outstanding research on the history of Jewish citizens
in Frankfurt.
“The work paints a highly differentiated
picture of the complex relationships of Jews among themselves and with
non-Jewish German society after the Shoah," said the jury, chaired by Professor
Mirjam Wenzel, Director of the Jewish Museum and honorary professor at Goethe
University, in praise of the winner. Freimüller's work, furthermore, has the
potential of becoming a standard work.
Before 1933, Frankfurt am Main had the
largest percentage of Jewish citizens in Germany, and its Jewish community was
the second largest in Germany following Berlin. In finance, education, science,
and through numerous associations and foundations, Jewish citizens influenced the
city of Frankfurt in a distinct way. At the end of the war in the spring of
1945, the persecution, deportation and murder of Jews had completely destroyed
this diverse culture. Had there once been almost 30,000 Jewish citizens in Frankfurt,
now only 100 to 200 remained in the destroyed city.
A larger number of Jewish “Displaced
Persons“ (DP) joined the few survivors who had quickly re-founded the Jewish
community after the war. These DPs were refugees from Eastern Europe who saw in
the American Headquarters in Frankfurt a gateway to their future lives. From
here, they hoped to be able to travel to America, Palestine or other countries.
But since this path was barred for the time being, thousands of Jewish DPs
lived for several years in a hurriedly set-up camp in Frankfurt-Zeilsheim. At
the same time, the first Frankfurt Jewish survivors began to return from exile,
having been expressly encouraged to do so by Frankfurt's Mayor Walter Kolb.
In his study, Tobias Freimüller depicts
how institutions and a social place for Jewish life were gradually able to be
established in Frankfurt in the following years. On the one hand, the city
serves as a typical example of Jewish post-war history in the Federal Republic
of Germany, as a place where the conflict situations of Jewish post-war history
can be seen under a magnifying glass. But Frankfurt was also an exception.
Under the protection of the American occupying forces, a network of Jewish
institutions was quick to form, later including an intellectual scene whose
lighthouse was the Institute for Social Research, which had returned from
exile. Nonetheless, the relationship between Jewish and non-Jewish citizens in
Frankfurt remained particularly conflictive. Highlights of these disputes were
the sensational blockade of the premiere of the play "Der Müll, die Stadt und der Tod" by Rainer Werner Fassbinder
by the Jewish community in autumn 1985, and the Börneplatz conflict in 1987.
Where, after the end of National
Socialism, and in what form did a memory of local Judaism still exist that
could be taken up? How should Jewish places of memory that still existed in the
city's topography be handled? How did the integration of the Holocaust survivors
who fled Eastern Europe after the end of the war succeed, and why did the
"second generation" of Jews since the 1960s articulate themselves so
clearly in Frankfurt in particular? German-Jewish post-war history appears in
the example of Frankfurt as a multi-faceted history of migration, conflict, and
new intellectual beginnings, out of which a new Jewish consciousness ultimately
developed in the 1980s.
The Rosl and Paul Arnsberg Prize from the
Polytechnic Foundation of Frankfurt am Main was created in 2008 and has now
been awarded for the sixth time. It is advertised internationally, and is
dedicated to outstanding research on the history of Jewish life in Frankfurt.
The prize is endowed with € 10,000.
Pictures may be downloaded here: http://www.uni-frankfurt.de/84238080www.uni-frankfurt.de/84238080
Caption: Tobias Freimüller was awarded the Rosl and Paul Arnsberg Prize from the
Polytechnic Foundation of Frankfurt am Main for his work on the history of
Frankfurt Judaism. (Credit: Polytechnic Foundation of Frankfurt am Main/Dominik
Buschardt)
Further information: Dr Tobias Freimüller, Deputy Director of the Fritz Bauer Institute, Goethe
University An-Institut, Westend
Campus, Tel- +49 69/798 322-31, E-Mail freimueller@em.uni-frankfurt.de, Homepage www.fritz-bauer-institut.de
Archaeologists at Goethe University conclude project in Stockstadt am Main
FRANKFURT. In an extensive project, archaeologists
at Goethe University processed and digitally recorded Roman artefacts from
Stockstadt am Main (Bavaria). The work lays the groundwork for future research
and a new conceptualizing of the museum in Stockstadt.
The Roman Stockstadt is above all
internationally known for its Mithras temple (mithraeum), the stone altar of
the Beneficiarii (beneficiarii consulares), a kind of military police and
customs office for the Roman governor, two bronze faces from paradehelmets of
horsemen, and a hoard of coins consisting of 1315 silver coins (denarii).
Today, these artefacts are stored and displayed in the Saalburg Museum, the Archaeological
Collection of the Bavarian State in Munich, and in the Stiftsmuseum Aschaffenburg.
Extensive excavations were only carried
out between 1885 and 1909, and some smaller ones after 1990. Most recently,
excavations in the Roman graveyard were conducted in 2011/2012. Since 2005, the
Roman site has been a part of the UNESCO World Heritage Site Upper German-Raetian
Limes (Obergermanisch-rätischer Limes).
The museums mentioned above are not the
only museums storing finds from Stockstadt; the Heimatmuseum Stockstadt possess
a collection of more than 6000 objects of Roman artefacts, including diverse
objects from daily life and military equipment, but also architectural
components from the fort’s fortification and well-preserved burial objects from
numerous graves. These finds originate mostly from rescue operations and chance
finds at construction sites from the 20th
century by volunteers and private citizens, as well as from official
excavations. The finds, some of whose are of international significance, are
largely unpublished and only exemplarily displayed.
The systematic archiving and indexing of these
inventories for science and the interested public was the goal of a
Bavarian-Hessian cooperative project involving the city Stockstadt a.M., Goethe
University Frankfurt, and the Landesstelle für die nichtstaatlichen Museen in
Bayern (State Office for Non-governmental
Museums in Bavaria), which was concluded after nine months at the end of
2019. The artefacts are now digitally recorded and researchable according to
current standards for cultural assets in a media database of the Landesstelle für die nichtstaatlichen Museen
in Bayern. Beginning in 2020, the database will be accessible online
through the Stockstadt homepage. To achieve this goal, the artefacts had to be
cleaned, sorted according to collection or find site and material, scientifically
identified (at least roughly), and dated. In addition, the objects were
photographed individually or in groups. This collection and securing of data
laid the groundwork for the archiving that accompanied entry of the data into
the media database. Each object was labelled with an inventory number.
All of this work was carried out by a small
team of students with the support of volunteers. The students thus had the
opportunity to gain material knowledge in their area of study and at the same
time obtain insight into practical museum work in the digital age. Dr Alexander
Reis from Obernburg am Main, who works as scientific assistant at the Institute
for Archaeological Sciences (Dept. II) headed the project; his employment was
made possible by third-party funding from the city of Stockstadt for this
project. He is a specialist in provincial Roman archaeology and received his
doctorate at the Goethe University in the Archaeology and History of the Roman
Provinces with the thesis “NIDA – Heddernheim in the 3rd Century AD – studies
on the end of the settlement” (Manuscripts of the Archaeological Museum
Frankfurt 24, Frankfurt a.M. 2010) under Professor Hans-Markus v. Kaenel.
The project has not only yielded an
appreciable added value for archaeological Limes research, it also forms the
basis for a future reconceptualization of the museum’s permanent exhibit. In
the course of the project, it was also possible to transfer the extensive
private collection of the local pharmacist Dr Fred Rattinger (1912-1981) to
public ownership. The ceremonial transfer of the collection took place on
December 2nd as part of a press event.
Pictures can be downloaded here: www.uni-frankfurt.de/83879025
Captions: Picture 1: Sigillata bowl from Gaul, 2nd Century AD; Picture 2: Roman grave from Stockstadt.
Credit: Goethe University
Further information: Professor Markus Scholz, Archeology and History of the Roman Provinces,
Institute for Archeological Scineces, Dept. II, Faculty 9, Westend Campus, Tel.
+49 (0)69 798 32265, m.scholz@em.uni-frankfurt.de