Light-inducible microRNA inhibitors used for the first time as local therapeutic agents
FRANKFURT.MicroRNAs are interesting target structures for new therapeutic agents. They can be blocked through synthetic antimiRs. However, to date it was not possible to use these only locally. Researchers at Goethe University Frankfurt have now successfully achieved this in the treatment of impaired wound healing with the help of light-inducible antimiRs.
MicroRNAs are small gene fragments which bond onto target structures in cells and in this way prevent certain proteins from forming. As they play a key role in the occurrence and manifestation of various diseases, researchers have developed what are known as antimiRs, which block microRNA function. The disadvantage of this approach is, however, that the blockade can lead to side effects throughout the entire body since microRNAs can perform different functions in various organs. Researchers at Goethe University Frankfurt have now solved this problem.
The research groups led by Professor Alex Heckel and Professor Stefanie Dimmeler of the Cluster of Excellence Frankfurt Macromolecular Complexes have developed antimiRs that can be activated very effectively over a limited local area by using light of a specific wavelength. To this purpose, the antimiRs were locked in a cage of light-sensitive molecules that disintegrate as soon as they are irradiated with light of a specific wavelength.
As a means of testing the therapeutic effect of these new antimiRs, the researchers chose microRNA-92a as the target structure. This is frequently found in diabetes patients with slow-healing wounds. They injected the antimiRs in the light-sensitive cage into the skin of mice and then released the therapeutic agent into the tissue with the help of light. Together the research groups were able to prove that pinpointed activation of an antimiR against microRNA-92a helps wounds to heal.
“Apart from these findings, which prove for the first time that wound healing can be improved by using antimiRs to block microRNA-92a, our data also confirms that microRNA-92a function is indeed only locally inhibited. Other organs, such as the liver, were not affected”, says Professor Stefanie Dimmeler, underlining the trials’ clinical significance.
The researchers now want to see whether they can also expand the use of light-inducible antimiRs to the treatment of other diseases. In particular they want to examine whether toxic antimiRs can attack tumors locally as well.
Publication: Tina Lucas, Florian Schäfer, Patricia Müller, Sabine A. Eming, Alexander Heckel & Stefanie Dimmeler: “Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice”, in: Nature Communications, publication date, doi: 10.1038/ncomms15162
Further information: Professor Dr. Stefanie Dimmeler, Institute of Cardiovascular Regeneration and Cluster of Excellence Frankfurt Macromolecular Complexes, Excellence Cluster Cardio-Pulmonary System, Faculty of Medicine, Frankfurt University Hospital, Tel.: +49(0)69-798-29475, firstname.lastname@example.org
Screening process for lead structures with optimized efficiencies
FRANKFURT.Organic light-emitting diodes (OLEDs) are promising candidates for flexible flat displays. By means of a screening process developed by chemists at Goethe University Frankfurt, it is now possible to identify more quickly lead structures with superior luminescence and charge-transport properties.
The rising demand for increasingly sophisticated smartphones, tablets and home cinemas is a growing challenge for display technology. At present, organic materials are the most effective way to master this challenge. In particular molecules from the class of materials known as polycyclic aromatic hydrocarbons (PAHs) can be used to produce large and mechanically flexible flat screens. They unite brilliant colours with high resolution and are at the same time low in energy consumption.
Chemists at Goethe University Frankfurt are currently working on new types of organic luminescent materials which owe their particularly promising properties to the introduction of boron atoms into the PAH scaffold. To date, the syntheses required have been extremely complex and time-consuming. A recently developed screening process, which makes a wide variety of boron-doped PAHs quickly and easily accessible, could in future alleviate this situation. The technique makes it possible to evaluate their potential as OLED materials. Only the most promising candidates will be examined more extensively in the next stage.
As the research group led by Professor Matthias Wagner at the Institute of Inorganic and Analytical Chemistry of Goethe University Frankfurt reports in the scientific journal “Angewandte Chemie”, the method is based on a three-component reaction: Two components remain unchanged in all reactions whilst the third is chosen from a broad range of cheaply available PAHs. The reactive boron-containing starting material plays an important role in the assembly of the molecular scaffold. In addition, it gives the compounds obtained the desired optoelectronic properties by increasing luminescence and improving the materials’ electrical conductivity.
“For a long time, it has mostly been pharmaceutical research which has profited from screening processes”, says doctoral researcher Alexandra John. “Yet it makes sense precisely in the dynamic and growing field of organic materials to use similar strategies to achieve results in a cost-efficient and resource-friendly way”. Professor Matthias Wagner adds: “Our development’s market relevance can also be seen by the fact that the Federal Ministry for Economic Affairs and Energy is giving our research work generous financial support.” The funding instrument behind it - WIPANO - supports the transfer of knowledge and technology through patents and norms and aims to ensure the commercial exploitation of innovative ideas and inventions generated by public-funded research by safeguarding and utilizing intellectual property. Wagner and John have already filed a patent for their process.
Alexandra John, Michael Bolte, Hans-Wolfram Lerner, and Matthias Wagner: A Vicinal Electrophilic Diborylation Reaction Furnishes Doubly Boron-Doped Polycyclic Aromatic Hydrocarbons, in: Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201701591.
A picture can be downloaded from: www.uni-frankfurt.de/66206458
Caption: A new screening process means that promising OLED lighting materials can be identified more efficiently.
Copyright: AG Matthias Wagner
Further information: Professor Dr. Matthias Wagner, Institute for Inorganic and Analytical Chemistry, Riedberg Campus, Tel.: +49(0)69-798-29156; Matthias.Wagner@chemie.uni-frankfurt.de
Proposal by young geoscientists and physicists shortlisted
Their own experiment on the International Space Station (ISS) is the dream of many young early career researchers. For some geosciences and physics students at Goethe University Frankfurt this could soon becoming intriguing reality. They answered a call by the German Aerospace Center and entered their own project proposal in the area of zero gravity.
A total of eight projects were selected from a large number of submissions. Three students from each project have now been invited by the centre in Bonn to present their concepts in person, including the EXCISS project of the student group in Frankfurt. EXCISS stands for Experiment on Chondrule Formation on the ISS. At the end of the selection procedure, German astronaut Alexander Gerst will take three experiments with him to the International Space Centre and conduct them there.
“What we want to solve with this experiment is nothing less than the origin of the most common solid objects in the early solar system”, reports group leader Tamara Koch. When our solar system was born about 4.56 billion years ago, the solar nebula was composed of gas and dust particles. These were made up either of calcium and aluminum-rich minerals or iron and magnesium-rich silicates. By means of a process as yet unexplained, these were suddenly heated up to several thousand degrees in the early phase of the solar system, only to solidify equally suddenly in droplet form, what are known as chondrules. This process has left researchers baffled up until today.
There are several hypotheses. For example, shock waves or flashes of lightning could have heated up the dust particles to such a high temperature. Another possibility could be a collision between asteroids. None of the three hypotheses has so far won through. The students want to examine now in the framework of the EXCISS project whether the chondrules in the dust-gas mix of the solar nebula could have evolved through high-energy lightning. The focus is on the iron and magnesium-rich silicates.
Tiny flashes of lightning in a weightless environment
“The idea behind this project is simple“, explains Tamara Koch. “We want to let dust particles collide in zero gravity under conditions such as prevailed in the solar nebula. Flashes of lightning are then repeatedly shot at the lumps of dust which have formed as a result. The lightning is created by discharging plate capacitors. What’s new about the idea is its implementation under realistic zero gravity conditions and with low gas pressure. Such experiments are not possible on Earth even in drop towers. The ISS offers a unique environment in which to test the lightning hypothesis.”
“Carrying out such a project in a small box of less than 15 centimeters edge length and with a 2-volt electricity supply is certainly a challenge”, says Yannik Schaper, who together with his fellow students is taking care of the physics side of the project.
“Only through close cooperation between geoscientists and physicists can the project be put into practice successfully”, explains Frank Brenker, Professor for Nanogeoscience and project initiator. “The students have done a great job here and produced a sound concept in a very short time frame. That’s why we weren’t really surprised to be among the last eight”, he reports.
The group is now eagerly awaiting the meeting in Bonn and hopes to be one of the three projects which is awarded funding and ultimately flies to the ISS. The project is supported by the working groups on Nanogeoscience (Professor Frank Brenker) and Crystallography (Professor Björn Winkler) as well as by the glassblowing workshop of the Department of Chemistry at Goethe University Frankfurt (Michael Röder). Sponsors willing to give the project their financial support are greatly welcomed.
Goethe University Frankfurt secures two ERC Advanced Investigator Grants / € 2.5 million each for five years
FRANKFURT.Two ERC Advanced Investigator Grants of the European Research Council to the amount of€2.5 million each are going to researchers at Goethe University Frankfurt. Biochemist and physician Professor Ivan Dikic and microbiologist Professor Volker Müller are very honoured that their pioneering research projects have been selected for this substantial financial support.
Environmentally friendly fuels
Volker Müller is one of the leading microbiologists worldwide in the field of microbial metabolism of microbes that grow in the absence of oxygen. His project centres on the production of biofuels with the help of bacteria that can use carbon dioxide as feedstock. Such fuels would have the advantage of making us independent of fossil fuels and reducing greenhouse gas emissions. For many years, Professor Müller’s research group at the Institute of Molecular Biosciences of Goethe University Frankfurt has been investigating a specific group of bacteria that convert carbon dioxide (CO2) and hydrogen (H2) or carbon monoxide (CO) to acetic acid in a fermentation process. The bacteria require neither light nor oxygen to do so.
What are known as acetogenic bacteria are already used on an industrial scale for exhaust gas fermentation American company LanzaTech. The aim here is primarily to render the exhaust gas harmless. Müller is already coordinating a pan-European consortium targeted at the optimization of gas fermentation. In the research project funded by the ERC, Müller wants now to further utilize the potential of Acetobacterium woodii. The bacterium can also process methanol or formic acid - both are cheap raw materials for biotechnology applications. Müller and his research group want to solve and then alter the metabolic pathways. The goal is to genetically modify acetogenic bacteria in such a way that they can produce environmentally friendly fuels and base chemicals on a large scale from various source materials.
New strategies to combat infectious diseases
It is the second time already that Ivan Dikic, who was born in Croatia, has been awarded an ERC Advanced Investigator Grant. He is one of the international pioneers in the area of ubiquitin research. Ubiquitin regulates many cellular processes; amongst others it controls the degradation of superfluous or harmful proteins and the repair of defective DNA, transmits signals within the cell and triggers cell death if damage cannot be controlled any more. In addition, ubiquitin has been recognized as being very important for fighting bacterial infections.
In his new ERC project, Dikic is investigating how bacteria manipulate the ubiquitin system of their host organism to their own advantage. In the focus are infections with Salmonella, Shigella and Legionella. Dikic’s research group at the Institute of Biochemistry II is e.g. searching for new signaling pathways which are activated by bacterial enzymes. They are employing high-resolution microscopy methods and cutting-edge mass spectrometry that allows the quantitative assessment of all cellular proteins and their ubiquitin modifications. By this approach, the cell biologists want to elucidate how various bacterial enzymes influence the severity and course of an infection and why serious secondary tissue damage sometimes occurs despite successful treatment with antibiotics. Such damage cannot only be caused by bacterial toxins, but also by signalling substances secreted by the host’s own immune cells following an infection. This secondary damage can be life-threatening.
In a second step, the researchers in Dikic’s group want to search for substances that actively interfere with this process and in particular limit tissue damage. To this purpose, Dikic is working together with partners in the pharmaceutical sector. The ultimate goal is to fully understand the role of the ubiquitin system in bacterial infections and to seize the newly obtained knowledge for developing new strategies for combating infectious diseases.
Pictures can be downloaded under the following link: www.uni-frankfurt.de/66113784
Further information: Professor Dr. Volker Müller, Institute of Molecular Biosciences, Faculty of Biological Sciences, Riedberg Campus, Tel.: +49(0)69-798-29507; -29508, Email: VMueller@bio.uni-frankfurt.de.
Professor Dr. Ivan Dikic; Media contact: Dr. Kerstin Koch, Institute of Biochemistry II, Faculty of Medicine, Frankfurt University Hospital, Tel.: +49(0)69-6301-84250, Email: email@example.com.
Event Horizon Telescope: Goethe University is participating via the ERC-project Black Hole Cam
As part of the collaboration "BlackHoleCam" the research group of Prof. Luciano Rezzolla of Goethe University Frankfurt contributes to the international Event Horizon Telescope (EHT) Collaboration, which is imagining for the first time the black-hole candidate at the Center of our Milky Way.
Frankfurt. The international Event Horizon Telescope (EHT) Collaboration, which is imaging for the first time the black-hole candidate at the center of our Milky Way, has a major research focus in Germany. A significant contribution to this experiment is part of “BlackHoleCam”, a German-Dutch experiment founded in 2014. The research group of Prof. Rezzolla at the Institute for Theoretical Physics at the Goethe University Frankfurt is part of the collaboration. BlackHoleCam is supported by the European Research Council via an ERC Synergy Grant of 14 Million Euros.
Due to the strong pull of gravity, not even light can escape from black holes, whose surface, i.e., the event horizon, cannot be observed directly. However, the boundary which separates photons that are trapped from those that can escape from the incredible gravitational pull is called the black-hole “shadow”, because it would appear as a shadow against a bright lit background. It is such a shadow that is the target of series of observations presently ongoing of Sgr A*, the name of the black-hole candidate in our Milky Way. During the observations, the researchers will analyze the radio emission emitted by Sgr A*, whose mass is 4.5 million times that of our Sun and whose shadow is about half of the size of the distance between the Sun and the Earth.
Despite being so massive, Sgr A* is also very far from us, at a 26,000 light years, making the angular size of the shadow extremely small. Measuring the emission from this surface is therefore equivalent to imaging an apple on the surface of the Moon. To accomplish this ambitious project several radio telescopes across the globe are connected and thus form a virtual telescope with a diameter comparable to the Earth. This technique is called Long Baseline Interferometry (VLBI).
The work of BlackHoleCam is lead by Prof. Luciano Rezzolla (ITP, Frankfurt), Prof. Michael Kramer (Max Planck Institute for Radio Astronomy, Bonn), and by Prof. Heino Falcke (Radboud-University Nijmegen, Netherlands); all of them are important contributors of the EHT collaboration. In the current observations of Sgr A*, network of radiotelescopes from Europe, the United States of America, Middle- and South America, and the South Pole telescope are participating at the same time. During the observations, each telescope records the data on hard disks which are shipped after the end of the campaign to one of the high-performance computer centers in the US or to Bonn. In these centers the individual data of the telescopes are combined by supercomputers and an image can be reconstructed.
This shadow image can be regarded as the starting point for the theoretical research of Prof. Rezzolla's group. Besides predicting theoretically what type of image scientists is expected to observe, the group in Frankfurt is also working on determining whether it will be possible to establish if Einstein’s theory of general relativity is the correct theory of gravity. There are several other theories of gravity besides the well-known one by Einstein and the observations of the black-hole shadow may help to identify the true one. Because of this, scientists in Frankfurt analyze the size and the geometry of the shadow and compare them to synthetic images generated on supercomputers which model accretion flows onto black holes..
These images are computed by solving the equations of relativistic magneto-hydrodynamics and tracing the orbit of photons around black holes in different theories of gravity using state-of-the art numerical tools developed in the group of Prof. Rezzolla. Comparing the synthetic shadow to the observed one may shed light on the existence of one of the most extreme predictions of Einstein’s theory of gravity: the existence of black holes. However, as Prof. Rezzolla remarks, “These observations represent a major step forward in the international attempt of understanding the nature of the dark and compact object at the centre of our Galaxy. However, they are just the first step and it is likely that many more observations of increasing precision will be necessary for finally settling this fundamental issue”.