A group of scientists has put together the puzzle pieces of a riboswitch-based regulatory process in the bacterium Bacillus subtilis
The survival of the cell is - apart from other important aspects - a question of timing: Scientists of Goethe University together with colleagues from other universities have now identified the different parts of this mechanism and introduced a model of the process.
One of the central tenets of biology is that information flows from DNA to RNA in order to encode proteins, which function in the cell. Arguably just as critical as the genetic code is the timing of this information flow. By producing the right RNA and right proteins at the right time, a cell can effectively strategize its survival and success. One such regulatory element, the riboswitch, has excited interest as a potential target for antibiotics. After over 10 years of research, Prof. Harald Schwalbe's research group at the Goethe University, in collaboration with the Landick group at the University of Wisconsin, Prof. Jens Wöhnert from Goethe-University’s Biology Department and the Süß group at the Technische Universität Darmstadt, has put together the puzzle pieces of a riboswitch-based regulatory process in the bacterium Bacillus subtilis, presenting the most extensive model of the timing of riboswitch action to date.
A riboswitch is a short piece of RNA that can fold into different structures, depending on whether or not a small messenger molecule is binds to it. In transcriptional riboswitches, these different structures signal the nearby RNA polymerase to continue producing RNA or to stop. In their recent publication in ELife, the Schwalbe group and their collaborators released molecular structures of the xpt-pbuX riboswitch in the off-position after synthesis and in the on-position upon binding by the small messenger molecule guanine. They also demonstrated that this switch to the on-position takes a certain amount of time. This sets a certain requirement on this regulatory process.
As RNA polymerase flies along a DNA strand, producing the corresponding RNA, it reaches the code for the xpt-pbuX switch, makes the riboswitch, and continues on. If guanine is not around, the RNA polymerase would detect the default off-position and halt synthesis. However, if guanine were to bind the riboswitch, the riboswitch would need to refold into the on-position, and RNA polymerase would have to wait long enough to detect the new conformation. Otherwise, it would always read "off", and that gene would never be read. Schwalbe and coworkers found that just such a pause does exist, and it's encoded into the DNA. After producing the xpt-pbuX switch, the RNA polymerase encounters this "pause site" on the DNA code and slows down, allowing the right amount of time for the riboswitch to refold.
This work provides the most in-depth kinetic model of riboswitch function to date and underscores the importance of pause sites in our understanding of riboswitches. As researchers consider using riboswitches as tools in synthetic biology applications, they will do well do keep the speed of the RNA polymerase in mind.
Publication: Steinert H, Sochor F, Wacker A, Buck J, Helmling C, Hiller F, Keyhani S, Noeske J, Grimm S, Rudolph MM, Keller H, Mooney RA, Landick R, Suess B, Fürtig B, Wöhnert J, Schwalbe H.; Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation.; Elife; 2017; doi: 10.7554/eLife.21297.
Further Information: Prof. Dr. Harald Schwalbe, Institute for Organic Chemistry, email: email@example.com.
Machos are only welcome when female mosquitofish are in a group
FRANKFURT.In evolution, a high sex drive does not always pay off. Female mosquitofish swim away from over-impetuous lovers because they leave them hardly any time to feed and also tend to injure their genitalia more often.
In some species, males invest virtually nothing in their offspring apart from sperm. So far, biologists believed that the most sexually active males in such species had an evolutionary advantage. But the ‘more mating, more offspring’ equation does not always hold in the case of the eastern mosquitofish (a small, livebearing freshwater fish) because the females also have a say, as behavioural researchers at Goethe University Frankfurt have now discovered.
“The starting point for our studies was the question why males in some animal species differ pronouncedly and consistently in their sexual activity levels even when they are exposed to identical environmental conditions and don’t need to compete”, explains Carolin Sommer-Trembo, who is dealing with the topic in her doctoral thesis. “We wanted to know how this variation in male behavioural types is maintained, although selection ought to oust males which display low or average levels of sexual activity.”
She chose the small and inconspicuous mosquitofish (Gambusia holbrooki) as a study object because they have sex and give birth to live offspring. Males have a penis-like mating organ on their underside which is long in comparison to their overall body size. To copulate, they swim up to the female from underneath in order to remain undiscovered for as long as possible.
To find out which males are interesting for female mosquitofish and whether the level of male sexual activity plays any role at all in their choice of partner, Carolin Sommer-Trembo and her colleagues Dr. David Bierbach (Leibniz Institute of Freshwater Ecology and Inland Fisheries, Berlin) and Professor Martin Plath (Northwest A&F University, Yangling) let females choose between males which displayed different levels of sexual activity. To exclude the possibility that specific males were chosen because of their appearance (morphology) or other behavioural characteristics and to control precisely the degree of sexual activity of the males, the researchers worked with computer-animated stimulus males which were presented to the females on monitors.
The result was that females preferred males which displayed a moderate level of sexual activity whilst they clearly avoided males with a greater sex drive. The researchers assume that this is due to cost-benefit considerations, since females who find themselves in the close vicinity of sexually very active males often not only suffer injuries to their genitalia but also scarcely have an opportunity to feed as they are constantly busy avoiding the males’ advances.
The situation is different when a group of females encounters a rampant male determined to mate. “Under natural conditions, female mosquitofish often form shoals to protect themselves from male harassment, just like other fish do to protect themselves from predators”, explains Carolin Sommer-Trembo. In the group, females showed far greater acceptance towards sexually very active males, since the cost-benefit ratio shifts under these circumstances.
The dependency of female choice on social context could explain why variation in male behavioural types is maintained amongst mosquitofish. And the experiments show that females include male sexual activity as a criterion in their choice of partner.
By the way: That swimming away from tempestuous lovers is a good idea when out on your own as a female mosquitofish does not appear to be instinctive but based on experience. When Sommer-Trembo conducted additional tests with virgin females, they were equally open to all types of male.
Sommer-Trembo, C., Plath, M., Gismann, J., Helfrich, C. & Bierbach, D.
Context-dependent female mate choice maintains variation in male sexual activity.
Royal Society Open Science; DOI: 10.1098/rsos.170303
A picture with a Creative Commons licence can be downloaded under:
The picture shows a female mosquitofish which is being pursued by a male in a typical manner. The male’s reproductive organ, what is referred to as the gonopod, is already extended and ready to “attack”. He swims up to the female from underneath in order to remain undiscovered for as long as possible.
Further information: Carolin Sommer Trembo, Institute of Ecology, Evolution and Diversity, Faculty of Biological Sciences, Riedberg Campus, Tel.: +49(0)69-798-42172, firstname.lastname@example.org.
EU funds further three networks for doctoral training at Goethe University Frankfurt
FRANKFURT. The European Union is funding three new projects - Innovative Training Networks (ITN) within the Marie Sklodowska-Curie Programme - for structured doctoral training at Goethe University Frankfurt. Such projects are very attractive for universities because they are open to all scientific topics and focus on basic research.
For the CLOUD-MOTION project coordinated by atmospheric researcher Professor Joachim Curtius, Goethe University Frankfurt has been awarded funding of € 500,000. This is a follow-up project from two previous doctoral researcher networks successfully coordinated by Professor Curtius since 2008.
In CLOUD-MOTION, doctoral researchers at 10 European institutions will investigate cloud formation from aerosols and ice particles in the atmosphere and their influence on the climate. A key focus is the comparison of intact areas of the atmosphere with those polluted as a result of human activities. Research work is based on experiments in a “cloud chamber” at CERN, the European Organization for Nuclear Research, in which different situations in the atmosphere can be simulated under laboratory conditions.
The ViBrANT Network, of which Goethe University Frankfurt is a member, is an interdisciplinary team of European infection researchers leading in their field worldwide. The network is working together for a better understanding of how viruses and bacteria attach to host cells. This will form the basis for developing highly specific diagnostic procedures, whereby one of the main priorities is the development of new diagnostic detection methods for multi-resistant pathogens. The 15 doctoral researchers will become acquainted with universities and industrial partners in seven European countries during their training and this will teach them how to convert findings from basic research as rapidly as possible into usable technologies that benefit patients with infectious diseases. € 500,000 have been made available for doctoral researchers at Goethe University Frankfurt.
Goethe University Frankfurt is also involved in the UbiCODE doctoral network, which is searching for new diagnostic markers and drug targets in the ubiquitin system. This small protein found throughout the body forms unexpectedly diverse and complex chains. The contribution of these chains to the regulation of protein functions and cellular quality control is, however, far from being fully understood. Malfunctions in this system can lead to diseases such as cancer, neurodegeneration, inflammatory conditions and multiple infections. Goethe University Frankfurt’s share of the funding is € 250,000.
With the approval of the three new ITNs, the University is continuing it success of the past years in this funding line. In 2016, five new projects started work. 18 ITNs are currently underway at Goethe University Frankfurt.
Further information: CLOUD-MOTION: Prof. Dr. Joachim Curtius, Department of Atmospheric and Environmental Sciences, Faculty of Geosciences and Geography, Riedberg Campus, Tel.: +49 (0) 69 798 40258, email@example.com
ViBrANT: Prof. Dr. Volkhard Kempf, Institute of Medical Microbiology and Infection Control, Faculty of Medicine, Niederrad Campus, Tel.: +49 (0) 69 6301-5019, firstname.lastname@example.org
UbiCODE: Prof. Dr. Ivan Dikic, Dr. Kerstin Koch, Institute of Biochemistry II, Faculty of Medicine, Niederrad Campus, Tel.: +49 (0)69 6301-84250, K.Koch@em.uni-frankfurt.de
New Emmy Noether Independent Junior Research Group at the Faculty of Law examines EU solidarity conflicts
FRANKFURT. A new Emmy Noether Independent Junior Research Group has started work at the Faculty of Law of Goethe University Frankfurt. The team headed by Dr. Anuscheh Farahat is dealing with the role played by constitutional courts in transnational solidarity conflicts.
The global financial crisis has severely disadvantaged countries in the European Union too – and some of them have still not recovered today. To rescue the euro, the European Member States were obliged to get a grip on the debts of countries such as Greece, Spain or Portugal. This demanded and continues to demand a lot of transnational solidarity. However, coping with the crisis leads time and again to conflicts in creditor and debtor countries since it raises legal issues on both sides. For example, Germany’s Federal Constitutional Court had to clarify, amongst others, to what extent the Bundestag (the German parliament) is obliged to approve Germany’s participation in relief actions; after all, budget decisions are down to parliament. In Portugal, on the other hand, what were referred to as “Troika measures”, which foresaw sharp cutbacks in employees’ income, landed before the national constitutional court, which was asked to clarify whether measures such as salary and pension cuts in the civil service were consistent with the constitution.
Are the courts the right institution to resolve such questions? Or might it not be the responsibility of a European-level entity or the parliaments? Or how else could the national courts be persuaded to take the perspective of other affected countries into account in their decisions? It is questions such as these which are being tackled by the new Emmy Noether research project “Transnational Solidarity Conflicts: Constitutional Courts as Fora for and Players in Conflict Resolution” that started recently. Project leader Dr. Anuscheh Farahat is convinced: “The crisis in the EU is in actual fact a crisis of transnational solidarity.” That is why she is investigating distribution and recognition conflicts in her project, which have become exacerbated in the EU during the course of the economic and financial crisis. Her work centres on what role national and European constitutional courts have played in these conflicts. How was the destructive potential of these conflicts institutionally channelled? Could new social order be brought about in the process? Or are other structures needed?
The Emmy Noether Independent Junior Research Group, which is made up of three early career researchers, will receive € 900,000 in funding from the German Research Foundation, initially until February 2020. Project leader Anuscheh Farahat studied in Frankfurt, Paris and Berkeley and completed her doctoral degree in 2011 at Goethe University Frankfurt with a thesis on migration law that has been awarded numerous prizes. In 2014 she became Senior Research Fellow at the Max Planck Institute for Comparative Public Law and International Law in Heidelberg. Her research interests are European and German constitutional law, German and international migration law as well as comparative constitutional law. A main focus of her current research work is questions related to the organization of public authority in transnational judicial areas.
A picture can be downloaded from: www.uni-frankfurt.de/66895847
Caption: Dr. Anuscheh Farahat heads the new Emmy Noether Independent Junior Research Group at Goethe University Frankfurt. She is investigating the role of constitutional courts in European solidarity conflicts. Photo: MPIL/Maurice Weiss
Further information: Dr. Anuscheh Farahat, email@example.com
Anesthetics cause certain areas of the brain to generate less information
FRANKFURT. To date, researchers assumed that anesthetics interrupt signal transmission between different areas of the brain and that is why we lose consciousness. Neuroscientists at Goethe University Frankfurt and the Max Planck Institute for Dynamics and Self-Organization in Göttingen have now discovered that certain areas of the brain generate less information when under anesthesia. The drop in information transfer often measured when the brain is under anesthesia could be a consequence of this reduced local information generation and not – as was so far assumed – a result of disrupted signal transmission between brain areas.
If only a few telephone calls are made in a city then it could be the case that several telecommunication systems have broken down – or it is nighttime and most people are asleep. The situation is similar in an anesthetized brain: if there is remarkably little information transfer between various areas of the brain then either signal transmission in the nerve fibers is blocked or certain areas of the brain are less active as far as the generation of information is concerned.
Patricia Wollstadt, Favio Frohlich, their colleagues from the Brain Imaging Center at Goethe University Frankfurt and researchers at the MPI for Dynamics and Self-Organization have now investigated this second hypothesis. As they have announced in the current issue of “PLOS Computational Biology”, they used ferrets to examine “source” brain areas from which less information was transmitted under anesthesia than in a waking state. They found that information generation under anesthesia was far more affected there than in the “target” brain areas to which the information was transferred. This indicates that it is the information available in the source area which determines information transfer and not a disruption in signal transmission. Were the latter the case, a far greater reduction could be expected in the target areas since less information “arrives” there.
“The relevance of this alternative explanation goes beyond anesthesia research, says Patricia Wollstadt, “since each and every examination of neuronal information transfer should categorically take into consideration how much information is available locally and is therefore also transferable.”
Publication: Patricia Wollstadt, Kristin K. Sellers, Lucas Rudelt, Viola Priesemann, Axel Hutt, Flavio Fröhlich, Michael Wibral: Breakdown of local information processing may underlie isoflurane anesthesia effects, in PLOS Computational Biology, http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005511
A picture can be downloaded from: www.uni-frankfurt.de/66792186
Photo: Stefan_Schranz/ pixabay, CC 0
Further information: Prof. Dr. Michael Wibral, Brain Imaging Center, Faculty of Medicine, Frankfurt University Hospital, Tel.: +49(0)69-6301-83193, firstname.lastname@example.org