Press releases archive 鈥� January 2020
Jan
27
2020
10:23
New development makes tiny structural changes in biomolecules visible聽
Superfast insights into cellular events
FRANKFURT. Even more detailed insights into the cell will be possible in future with the help of a new development in which 51猎奇 was involved: Together with scientists from Israel, the research group led by Professor Harald Schwalbe has succeeded in accelerating a hundred thousand-fold the nuclear magnetic resonance (NMR) method for investigating RNA.
In the same way that a single piece of a
puzzle fits into the whole, the molecule hypoxanthine binds to a ribonucleic
acid (RNA) chain, which then changes its three-dimensional shape within a
second and in so doing triggers new processes in the cell. Thanks to an
improved method, researchers are now able to follow almost inconceivably tiny
structural changes in cells as they progress 鈥� both in terms of time as well as
space. The research group led by Professor Harald Schwalbe from the Center for
Biomolecular Magnetic Resonance (BMRZ) at 51猎奇 has succeeded,
together with researchers from Israel, in accelerating a hundred thousand-fold the
nuclear magnetic resonance (NMR) method for investigating RNA.
鈥淭his allows us for the first time to
follow the dynamics of structural changes in RNA at the same speed as they
occur in the cell,鈥� says Schwalbe, describing this scientific breakthrough, and
stresses: 鈥淭he team headed by Lucio Frydman from the Weizmann Institute in
Israel made an important contribution here.鈥�
The new types of NMR experiments use water
molecules whose atoms can be followed in a magnetic field. Schwalbe and his
team produce hyperpolarized water. To do so, they add a compound to the water
which has permanently unpaired electron radicals. The electrons can be aligned
in the magnetic field through excitation with a microwave at -271掳C. This
unnatural alignment produces a polarization which is transferred at +36掳C to
the polarization of the hydrogen atoms used in the NMR. Water molecules
polarized in this way are heated in a few milliseconds and transfered, together
with hypoxanthine, to the RNA chain. The new approach can in general be applied
to observe fast chemical reactions and refolding changes in biomolecules at
atomic level.
In particular the imino groups in RNA can
be closely analyzed using this method. In this way, the researchers were able
to measure structural changes in RNA very accurately. They followed a small
piece of RNA from Bacillus subtilis, which changes its structure during
hypoxanthine binding. This structural change is part of the regulation of the transcription
process, in which RNA is being made from DNA. Such small changes at molecular
level steer a large number of processes not only in bacteria but also in
multicellular organisms and even humans.
This improved method will in future make
it possible to follow RNA refolding in real time 鈥� even if it needs less than a
second. This is possible under physiological conditions, that is, in a liquid
environment and with a natural molecule concentration at temperatures around 36
掳C. 鈥淭he next step will now be not only to study single RNAs but hundreds of
them, in order to identify the biologically important differences in their refolding
rates,鈥� says Boris F眉rtig from Schwalbe鈥檚 research group.
Publication: Mihajlo Novakovic, Gregory L. Olsen, Gy枚rgy Pint茅r, Daniel Hymon, Boris
F眉rtig, Harald Schwalbe, Lucio Frydman: A 300-fold enhancement of imino nucleic
acid resonances by hyperpolarized water provides a new window for probing RNA
refolding by 1D and 2D NMR, PNAS, 16 January 2020
A
picture can be downloaded from:
Caption: Frankfurt researchers followed the movements of this tiny molecule 鈥� just two-thousandths of the thickness of a piece of paper. The RNA aptamer changes its structure when it binds hypoxanthine. The green nucleobases change shape particularly quickly, the ones coloured blue more slowly. The grey regions do not change.
Further
information: Professor Harald Schwalbe, Center for
Biomolecular Magnetic Resonance (BMRZ),
http://www.bmrz.de/, Institute of Organic Chemistry and Chemical Biology, Riedberg
Campus, Tel.: +49(0)69-798-29737 or -40258, e-mail:
schwalbe@nmr.uni-frankfurt.de.
Jan
24
2020
14:29
Reported reduction of HFC-23 did not happen
Further increase in potent greenhouse gas detected聽
FRANKFURT. According to the two main producers 鈥� China and India 鈥� the release of the potent greenhouse gas HFC-23 into the atmosphere should have almost completely stopped by 2017. However, the reality is that a team of atmospheric researchers led by the University of Bristol has measured record levels. Dr Kieran Stanley, lead author of the study published in the current issue of 鈥淣ature Communications", has been working at 51猎奇 for six months.
Over the past two decades, researchers have monitored the concentration of the hydrofluorocarbon HFC-23 very closely. 鈥淚t is a very potent greenhouse gas: The emission of one tonne of this substance does just as much damage as the emission of 12,000 tonnes of carbon dioxide," says atmospheric researcher Professor Andreas Engel from 51猎奇. HFC-23 primarily occurs as an unwanted by-product in the manufacture of the refrigerant HCFC-22.
In 2015 India and China, which are considered the main emitters, announced ambitious plans to abate their factory emissions and in 2017 they reported that almost no more HFC-23 was being vented to the atmosphere. This would mean that emissions of this greenhouse gas into the atmosphere between 2015 and 2017 ought to have shown a 90 percent reduction. However, as the international team now reports, emissions have risen further and in 2018 reached an all-time high.
The reduction of HFCs is part of the Kigali Amendment to the Montreal Protocol agreed in 2016. It entered into force in January 2020. Although China and India have not ratified the Amendment, by their own account they had achieved a massive reduction in emissions. 鈥淥ur study indicates that China has not managed to reduce HFC-23 as reported," concludes Dr Kieran Stanley, who conducted the measurements at the University of Bristol in the framework of the international AGAGE measurement network. Additional measurements will show whether India has successfully implemented its abatement programme.
鈥淭his is not the first time there's been controversy about HFC-23 emissions," says Kieran Stanley ruefully. With the United Nations Framework Convention on Climate Change, between 2005 and 2010 the industrial nations created incentives for emerging countries to reduce their emissions. Although emissions of this hazardous greenhouse gas did indeed decrease during that period, the system backfired: Manufacturers did not optimize their processes but instead produced more harmful by-products in order to pocket more funds for destroying them.
The Institute for Atmospheric and Environmental Sciences at 51猎奇, where Kieran Stanley is now working as a postdoctoral researcher, has measured a large number of halogenated trace gases at its Kleiner Feldberg measuring station at regular intervals since 2013. Since recently, these measurements are part of the AGAGE network.
Publication: K. Stanley, D. Say, J. M眉hle, C. Harth, P. Krummel, D. Young, S. O'Doherty, P. Salameh, P. Simmonds, R. Weiss, R. Prinn, P. Fraser and M. Rigby: Increase in global emissions of HFC-23 despite near-total expected reductions, in Nature Communications,
Further information: Dr Kieran Stanley, Institute for Atmospheric and Environmental Sciences, Riedberg Campus, Tel.: +49(0)69-798-40249; stanley@iau.uni-frankfurt.de
Jan
15
2020
11:08
Single-molecule microscopy visualises the dance of receptors
Visualising Molecular Patterns of Membrane TNF 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 伪 (TNF伪). Now, for the first time, researchers
from 51猎奇 have visualised the molecular organisation of individual
TNF伪 receptor molecules and the binding of TNF伪 to the cell membrane in cells
using optical microscopy.
Before
TNF伪 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. 鈥淔or
TNFR1 in the membrane, the binding of TNF伪 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 f眉r Krebskranke
Kinder at 51猎奇.
In particular, CRD1 of the TNFR1 makes it
possible for TNF伪 to 鈥渁ttach". Researchers already knew that TNFR1 molecules cluster
in a fashion similar to a dance, in which two, three or more partners grasp
hands 鈥� with the dimers, trimers or oligomers consisting of single TNFR1 molecules
鈥� in the case of TNFR1. This kind of 鈥渟tructural reorganization" also takes
place when there is no TNF伪 present. 鈥淒espite the significance of TNF伪 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 51猎奇. 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 51猎奇, Harald Wajant from the University
Hospital W眉rzburg and Darius Widera from University Reading/UK, they were able to
observe the dance of the TNF伪 receptors. Financial support was provided by the
Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research Centre
807 鈥淭ransport and Communication across Biological Membranes".
As the researchers report in the current issue of
鈥淪cience Signalling", membrane TNFR1 receptors exist as monomers and dimers in
the absence of TNF伪. However, as soon as TNF伪 binds TNFR1, receptor trimers and oligomers are formed
in the membrane. The researchers also found indications for mechanisms that
determine cell fate independently of TNF伪. These findings could be relevant for
cancer or and inflammatory diseases such as rheumatoid arthritis. 鈥淚t 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
TNF伪-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