Press releases – 2015

FRANKFURT. Neurons and blood vessels often traverse the body side by side, a fact observed as early as the 16^th century by the Flemish anatomist Andreas Vesalius. Only over the last ten years, however, researchers have discovered that the growth of neuronal and vascular networks is controlled by the same molecules. Prof. Amparo Acker-Palmer, a pioneer in this area, performs groundbreaking research on the communication between neurons and blood vessel cells in the brain. She hopes to use her findings to gain important insights into brain diseases such as dementia and mental illness. The European Research Council will fund her project with an Advanced Investigator Grant of 2.5 million Euros over the next five years.

“Most interesting is the interaction between neurons and blood vessels in the cerebral cortex. To date, we know very little about how neurons communicate with endothelial cells in order to structure a functional network in the brain.” explains Acker-Palmer. She plans to assess these processes in the layering of the cerebral cortex during embryonic development. Here, neuronal cells migrate in an inside out manner, while blood vessels grow in the opposite direction, from the pial surface towards the ventricular surface. Since these two growth processes are coordinated, Acker-Palmer suspects that they are controlled by the same signaling molecules. How dysfunction in the crosstalk may lead to cognitive impairments is one of the focuses of her research.

As model organisms her team uses genetically altered mice and zebrafish. Translucent zebrafish are the best suitable vertebrate model to visualize in vivo the dynamic events of cell-to-cell communication at the neurovascular interface. High-resolution electron microscopes will also be used to study these close connections between endothelial cells in the blood capillaries and glial cells at the blood-brain barrier. Glial cells wrap around the blood capillaries and prevent harmful substances from the blood stream from entering the brain.. Acker-Palmer and her team aim at deciphering the molecular signaling pathways regulating the neurovascular interface. “If we can intervene in the mechanism and temporarily open the blood-brain barrier, we can insert active agents and find new approaches for treating dementia and mental illness,” says the neurobiologist.

Amparo Acker-Palmer, born in Sueca, Valencia, Spain in 1968, studied biology and biochemistry at the University of Valencia, where she obtained her PhD in 1996. Then she moved to the European Molecular Biology Laboratory (EMBL) in Heidelberg to perform her postdoctoral work. In 2001, she moved to Martinsried, near Munich, to head an independent junior research group on signal transduction at the Max Planck Institute for Neurobiology. In 2007, she became Professor at the “Macromolecular Complexes” Center of Excellence at the Goethe University Frankfurt. Acker-Palmer is the Chair of the Molecular and Cellular Neurobiology Department at Goethe University Frankfurt since 2011. She received a Gutenberg Research College (GRC) fellowship from Johannes Gutenberg University Mainz in 2012, and she one of the leading scientists in the Rhine-Main Neuroscience Network (rmn2). In 2014, Acker-Palmer joined the Max Planck Society as Max Planck Fellow at the MPI for Brain Research in Frankfurt. Amparo Acker-Palmer is member of the Leopoldina German Academy of Natural Scientists and the Academia Europaea. She received the Paul Ehrlich Award for Young Scientists in 2010.

Pictures are available for download here: www.uni-frankfurt.de/55539781

Captions

Prof. Amparo Acker-Palmer.

Mouse brain: The microscope image of a mouse brain illustrates the close interaction between neurons (green), astrocytes (blue), and blood vessels (red) in the brain. The various cell populations appear in a specific pattern and interact with the neighboring cells.

Zebrafish:  In vivo-Imaging of the blood circulation system in a three-day-old zebrafish larva. The left picture shows a side view of the head, the middle picture a side view of the trunk and the right picture a back view of the head. Fluorescent reporter genes reveal that the blood vessels (green) are fully formed at this point. The individual blood cells (red) can also be seen circulating in the blood vessels.

Information:  Prof. Amparo Acker-Palmer, Institute of Cellular Biology and Neuroscience, Buchmann Institute of Molecular Life Sciences, Campus Riedberg, Tel.: (069) 798-42563, Acker-Palmer@bio.uni-frankfurt.de.

FRANKFURT. About 70 percent of our genes provide the blueprint for biomolecules whose function is only now being discovered – non-coding RNAs. Instead of being translated into proteins, they seem to perform steering functions in the body. Stefanie Dimmeler was one of the first researchers to prove that the sub-group of micro-RNAs plays a role in regenerating blood vessels. She has now received the coveted ERC Advanced Investigator Grant from the European Research Council (ERC), which will allow her to study another large group of non-coding RNAs. She believes that this group plays a role in creating heart attacks, strokes and cancer. ERC has awarded her 2.5 million Euros over the next five years.

“If you asked me what was special about the evolutionary development of human beings, I would say it´s the more than 30,000 non-coding RNA, most of which we only share with primates,” says Stefanie Dimmeler. From the perspective of her research area, cardiovascular regeneration, it is especially noteworthy that vascular illnesses like arteriosclerosis, which causes heart attacks, only occur in their typical form in humans. There are many indicators that long, non-coding RNAs, lncRNAs for short, control these illnesses. They affect the inside layer of the blood vessels, known as endothelial cells, and help supply the organs and tissues with oxygen and nutrients.

The technologies used to track these lncRNAs and their complex functions are much more complicated than finding proteins. Dimmeler and her working group identified two candidates, Angiolnc1 and Angiolnc2, that regulate the functions of endothelial cells. Now she wants to study the molecular epigenetic mechanisms that these two lncRNAs use to trigger vascular illnesses. The goal of this research is to identify new treatments for preventing arteriosclerosis, in order to reduce the incidence of heart attacks and strokes.

In the third part of her project, Dimmeler will study whether ring-shaped lncRNAs, which have special protection once they are released into the blood, can be used as biomarkers for identifying illnesses in the vascular system or the heart. To this end, she will work with her group to develop tests that can be used to find these biomolecules in patients’ blood during the various stages of cardiovascular illnesses.

Prof. Stefanie Dimmeler, born in 1967, studied Biology at the University of Constance, where she received her doctorate in 1993. After two years as a research assistant at the University of Cologne, she went to Goethe University, where she was promoted to professor in 1998 in the Department of Experimental Medicine. In 2001, she accepted a position as a professor in the Molecular Cardiology Department at Goethe University. She has been the Director of the Institute of Cardiovascular Regeneration, in the Center for Molecular Medicine, since 2008. She is the co-speaker of the DFG-funded “Cardiopulmonary Systems” Excellence Cluster, the “LOEWE Center for Cell and Genetic Therapy” funded by the State of Hesse, and the German Center for Cardiovascular Research (DZHK) funded by the German Ministry for Education and Research (BMBF) at the Rhine-Main site. She is a member of the Macromolecular Complexes Excellence Cluster as well as several specialized research areas. From 2008 to 2012, she was a member of the German Ethics Commission. Stefanie Dimmeler has received numerous research prizes, including the renowned Gottfried Wilhelm Leibniz Prize from the German Research Foundation and the Ernst Jung Prize for Medicine.

Pictures are available for download here: www.uni-frankfurt.de/55538604

Captions

Prof. Stefanie Dimmeler.

Blood vessels: An image of blood vessels in the heart (shown in red). The large vessel is surrounded by smaller vessels (capillaries). The nuclei are shown in blue, and the neurons are green.

Information:  Prof. Stefanie Dimmeler, Institute for Cardiovascular Regeneration, Niederrad Campus, Main Office: Claudia Herfurth, Tel.: (069) 6301-6667, herfurth@med.uni-frankfurt.de.

FRANKFURT. A quantum state predicted by the Russian theoretician Vitaly Efimov 40 years ago has been discovered by physicists of the Goethe University in a molecule consisting of three helium atoms. The molecule is of enormous spatial extent and exists mainly in the classically forbidden tunneling region, explain the researchers in the current edition of the journal “Science”.

In 1970, Vitaly Efimov analysed a three-body quantum system in which the attraction between two bodies reduced such that they become unbound. His prediction was that instead of breaking up, the molecule consisting of three particles can support an infinite number of bound states with huge distances between the binding partners. "Every classical notion as to why such a structure remains stable fails here", explains Prof. Reinhard Dörner, head of the research group at the Institute for Nuclear Physics.

This counter-intuitive prediction led to the currently booming field of "Efimov physics". It soon became apparent that a system consisting of three helium atoms, a so-called trimer, would be the prime example of this quantum mechanical effect. But all experiments conducted to prove the existence of the gigantic, extremely weakly bound helium system failed.

In 2006, physicists at the University of Innsbruck first found indirect indications of Efimov systems in cold quantum gases of caesium atoms. In the atom traps they used, the interaction between the particles can be externally controlled. Efimov systems, however, as soon as they appear, are ejected from the artificial environment of the trap and fall apart unseen.

The Frankfurt physicist Dr. Maksim Kunitski, of the research group of Prof. Dörner has now produced a stable Efimov system consisting of three helium atoms, by pressing gaseous helium at a temperature of only eight degrees above absolute zero through a tiny nozzle  into a vacuum. In this ultracold molecular beam, helium molecules with two, three or more helium atoms are formed. By diffraction of the molecular beam at a super-fine transmission grating, the physicist was able to spatially separate the trimers.

The researchers created an exploded view of this Efimov state which directly show the structure of and, in particular, the distances between the atoms in the trimer. They ionized each helium atom of the molecule with the help of a laser beam. Due to the electrostatic repulsion, the now triply positively charged trimer broke apart explosively. Subsequently, using the COLTRIMS microscope developed at the Goethe University, researchers measured the momenta of the helium ions in three-dimensions, which allowed to reconstruct the geometry of the trimer. 

In collaboration with the theoretician Doerte Blume of Washington State University in the USA, Maksim Kunitski found out that only one of the many possible Efimov states had in fact occurred naturally in the molecular beam. The distances between bonds in the huge molecule extend to more than 100 angstroms (compared to a mere two angstroms in a water molecule). Thereby, the helium atoms do not form an isosceles triangle, but are arranged asymmetrically. That correlates well with the theoretical predictions that have already existed for many years.

"This is the first stable Efimov system that has ever been discovered. The three-body system flies through the laboratory inside the vacuum chamber without further interaction and without the need for external fields", Dörner explains. "Maksim Kunitski has conducted this ground breaking work in a laser laboratory at the Goethe University Frankfurt. He did not need a big machine to accomplish this."

"The Efimov state is not an exotic special case, but rather an example of a universal quantum effect that plays an essential role in many areas of physics", Kunitski explains. Examples of this are cold atoms, clusters, nuclear physics and recently also solid-state physics. Moreover, there are also first reports about its significance in biology.

Reinhard Dörner could afford to tackle a research project that was so risky with respect to its prospects of success because in 2009 the German Research Foundation (DFG) made 1.25 million Euros available as part of its Koselleck programme. "It was a rather bold plan", says Dörner in retrospect, "but now, at the end of the project and really only because the DFG provided me with this large amount for a risky project without detailed planning – the search was successful."

Publication:

M. Kunitski et al.: Observation of the Efimov state of the helium trimer, in Science, 1. Mai 2015, DOI: 10.1126/science.aaa5601

You can find images for downloading at: link

Captions:

1)  Efimov trimer in a gas beam of other particles.  The three helium atoms form an acute triangle, their distance from the quantum cloud, shown in yellow, amounts to a hundredfold of the size of the atoms.    

2) Dr. Maksim Kunitski at the Frankfurt COLTRIMS microscope with which he discovered the Efimov state of the helium trimer.

Information: Prof. Reinhard Dörner, Institut für Kernphysik, Campus Riedberg, Phone +49 (0)69 798-47003, doerner@atom.uni-frankfurt.de.

Scientists from the Goethe University (GU) Frankfurt, the European Molecular Biology Laboratory (EMBL) Heidelberg and the University of Zurich explain skin fusion at a molecular level and pinpoint the specific molecules that do the job in their latest publication in the journal Nature Cell Biology.

In order to prevent death by bleeding or infection, every wound (skin opening) must close at some point. The events leading to skin closure had been unclear for many years. Mikhail Eltsov (GU) and colleagues used fruit fly embryos as a model system to understand this process. Similarly to humans, fruit fly embryos at some point in their development have a large opening in the skin on their back that must fuse. This process is called zipping, because two sides of the skin are fastened in a way that resembles a zipper that joins two sides of a jacket.

The scientists have used a top-of-the-range electron microscope to study exactly how this zipping of the skin works. “Our electron microscope allows us to distinguish the molecular components in the cell that act like small machines to fuse the skin. When we look at it from a distance, it appears as if skin cells simply fuse to each other, but if we zoom in, it becomes clear that membranes, molecular machines, and other cellular components are involved", explains Eltsov.

“In order to visualize this orchestra of healing, a very high-resolution picture of the process is needed. For this purpose we have recorded an enormous amount of data that surpasses all previous studies of this kind”, says Mikhail Eltsov.

As a first step, as the scientists discovered, cells find their opposing partner by “sniffing” each other out. As a next step, they develop adherens junctions which act like a molecular Velcro. This way they become strongly attached to their opposing partner cell. The biggest revelation of this study was that small tubes in the cell, called microtubules, attach to this molecular Velcro and then deploy a self-catastrophe, which results in the skin being pulled towards the opening, as if one pulls a blanket over.

Damian Brunner who led the team at the University of Zurich has performed many genetic manipulations to identify the correct components. The scientists were astonished to find that microtubules involved in cell-division are the primary scaffold used for zipping, indicating a mechanism conserved during evolution.

“What was also amazing was the tremendous plasticity of the membranes in this process which managed to close the skin opening in a very short space of time. When five to ten cells have found their respective neighbors, the skin already appears normal”, says Achilleas Frangakis from the Goethe University Frankfurt, who led the study.

The scientists hope that their results will open new avenues into the understanding of epithelial plasticity and wound healing. They are also investigating the detailed structural organization of the adherens junctions, work for which they were awarded a starting grant from European Research Council (ERC).

The original publication

Nature Cell Biology: Quantitative analysis of cytoskeletal reorganisation during epithelial tissue sealing by large-volume electron tomography, Eltsov, Dubé, Yu, Pasakarnis, Haselmann-Weiss, Brunner and Frangakis, 2015, AOP 21 April 2015, DOI 10.1038/ncb3159

http://www.uni-frankfurt.de/55227362

Figure legend: Perspective view of the zipping area with 17 skin cells "zipping". Membranes are colored in shades of brown and green to discriminate individual skin cells coming from the left or the right. The cells expand various types of protrusions in all directions to find their respective neighbor.

If the skin cells are computationally removed the shaping of the cells underneath is visualized, with the sealing of the skin visible in the back.

Information: Prof. Achilleas Frangakis, Institute for Biophysics, Cluster of Excellence Macromelecular Complexes, Goethe University, Phone +49(0)69 798-46462, achilleas.frangakis@biophysik.org.

FRANKFURT.Optogenetics is a new field of research that introduces light-sensitive proteins into cells in a genetically targeted manner, for example, to obtain information on signalling pathways and the function of neurons in a living organism. A new priority program supported by the German Research Foundation (DFG) under the auspices of Goethe University has now set itself the goal of developing the next generation of optogenetic tools and expanding their application both in basic research and also for medical purposes. DFG will provide six million Euros in funding for the programme over the next three years.

"We see our role as a pathfinder, to build a scientific network for optogenetics in Germany," says Prof. Alexander Gottschalk, spokesperson for the priority programme "Next generation optogenetics: Tool development and applications". After an application phase in the autumn of 2015, between 30 and 40 scientists from different universities will become involved; primarily biophysicists, cell biologists, chemists, medical scientists, and "photo-biologists." These are the types of specialists who will search for new, light-sensitive proteins, which will be introduced into cells and act like light switches to turn cellular processes on and off.

"Optogenetics already has many applications in basic research, but as a technology it is still in its infancy," explains Gottschalk. In order to achieve more widespread use of optogenetics in cell biology and neurobiology, the researchers want to develop new optogenetic tools. These will have higher light sensitivity, clarify the processes within individual cells and between different cells, and ultimately also be tested in animal models. This is necessary, especially with regard to medical applications; for example, for the enabling treatment of certain vision and hearing impairments or aspects of previously incurable diseases, such as Parkinson’s disease, seizure disorders, or cardiac diseases.

The scientists are placing special importance on informing the public about the opportunities and risks of optogenetics. This will be done through intelligible presentations for the lay public, and through articles on websites such as www.OpenOptogenetics.org, http://dasgehirn.info, and the future website of the research programme.

Information: Prof. Alexander Gottschalk, Institute for Biochemistry, Campus Riedberg, Tel.: (069) 798-42518, a.gottschalk@em.uni-frankfurt.de.

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