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Pre-product for innovative biofuels/Two patents filed
FRANKFURT.Short-chain fatty acids are high-value constituents of cosmetics, active pharmaceutical ingredients, antimicrobial substances, aromas or soap. To date, it has only been possible to extract them from crude oil by chemical means or from certain plants, such as coconut, using a complex process. Research groups led by Professor Martin Grininger and Professor Eckhard Boles at Goethe University Frankfurt have now succeeded in producing such fatty acids in large quantities from sugar or waste containing sugar with the help of yeasts. The process is simple and similar to that of beer brewing.
As the researchers reported in the latest issues of the renowned journals “Nature Chemical Biology” and “Nature Communications”, the short-chain fatty acids are also much sought after as a pre-product for fuels. “The new technology can be a key step to finding an alternative approach, using yeasts, to innovative types of biofuels whose properties almost equate to those of fossil fuels”, explains Eckhard Boles from the Institute of Molecular Biosciences.
The fatty acids produced by plants and animals are to a large extent made up of chains of eighteen carbon atoms. That means they are longer than the short-chain compounds required. In living cells, large protein complexes - fatty acid synthases - produce fatty acids by joining nine building blocks of two carbon atoms in an eight-cycle process. Martin Grininger, Lichtenberg Professor of the Volkswagen Foundation at Goethe University Frankfurt and research group leader at the Buchmann Institute for Molecular Life Sciences (BMLS), was involved in solving the three-dimensional structure of the fatty acid synthases. His extensive know-how in this field allowed him to intervene in their mode of action.
“First we examined how the fatty acid synthase counts cycles in order to decide when the chain is finished. We found a type of ruler which measures the length of the fatty acid”, explains Martin Grininger. “We modified this ruler in such a way that the fatty acid synthase measures incorrectly and releases shorter chains. All this took place first of all on the computer and in the test tube.”
Together with Eckhard Boles, who is conducting research on yeast metabolism at the neighbouring biocentre, the idea evolved to use Grininger’s modified fatty acid synthases in yeasts. “These yeasts all at once started to secrete short-chain fatty acids in remarkable quantities”, reports Boles. “Like in beer brewing, we can use these now to produce - instead of alcohol - high-quality short-chain fatty acids.” Grininger and Boles add: “This development is just the start. We want now, through similar modifications on other large enzyme complexes, that is, polyketide synthases, to synthesize other new types of molecule for the chemical and pharmaceutical industry which are not readily available otherwise.”
Goethe University Frankfurt has protected these developments by filing two European and international patents and is now looking for licensees for commercial applications.
Grininger and Boles are currently developing their technology further and in different directions. The aim of the “Chassy” project funded by the European Commission is to scale up the technology for industrial use. In addition, the LOEWE project “MegaSyn” financed by the Federal State of Hesse focuses on the production of further chemical compounds through the modification of polyketide synthases. And in the “Alk2Bio” project funded by the Federal Ministry of Food and Agriculture yeasts are being enhanced in such a way that they produce octanol and heptane biofuels from short-chain fatty acids.
Publications: Gajewski, J., Buelens, F., Serdjukow, S., Janßen,M., Cortina, N., Grubmüller, H. and Grininger, M. (2017) Engineering fatty acid synthases for directed polyketide production. Nat. Chem. Biol. doi:10.1038/nchembio.2314.
Gajewski, J., Pavlovic, R., Fischer, M., Boles, E. and Grininger, M. (2017) Engineering fungal de novo fatty acid synthesis for short chain fatty acid production. Nat. Commun. doi:10.1038/NCOMMS14650. http://rdcu.be/pX6c
A photograph can be downloaded from:www.uni-frankfurt.de/65728223
Caption: A modified fatty acid synthase (illustrated schematically in the blue box on the basis of its synthetic properties) can induce short-chain fatty acid production in a yeast cell. Synthesis can be compared with a multistep industrial process. By means of targeted modifications to the natural synthesis, individual processes are accelerated or slowed down (green and red arrows) in order to trigger premature release of short-chain fatty acids.
Further information: Professor Martin Grininger, Lichtenberg Professor of the Volkswagen Foundation, Institute for Organic and Chemical Biology and Buchmann Institute for Molecular Life Sciences (BMLS), Riedberg Campus, Tel.: +49(0)69-798-42705; firstname.lastname@example.org
Professor Eckhard Boles, Institute of Molecular Biosciences, Riedberg Campus, Tel.: +49(0)69-798-29513, email@example.com
First tumor-specific study among patients with advanced-stage cancer
FRANKFURT. Walking or jogging helps patients with advanced gastrointestinal cancer to cope better with the side effects of chemotherapy. This has now been shown by a study conducted by Katrin Stücher in the framework of her doctorate at the Department of Sports Medicine of Goethe University Frankfurt.
Exercise as a therapy to complement chemotherapy has a positive effect on muscles, balance and tumor-related fatigue syndrome. Patients tolerate the therapy better and experience less disease recurrence (relapses) later on. This has already been substantiated by many studies in the past. However, these examined patients in the early stages of their illness and did not differentiate between various types of tumor.
The study, a joint initiative of the Department of Sports Medicine headed by Professor Winfried Banzer and of Medical Clinic I together with the Gastrointestinal Centre of Agaplesion Markus Hospital in Frankfurt, both led by Professor Axel Dignaß, shows that patients with an advanced gastrointestinal tumor can also profit from exercise therapy. In accordance with the recommendations of the American College of Sports Medicine, the participants exercised either three times a week for 50 minutes or five times a week for 30 minutes at a pace which they considered to be “slightly strenuous”. If they were unable to manage this, then they were allowed to shorten their training sessions on the basis of a standardized model.
“For some patients, it was difficult to carry out the walking or jogging program in accordance with the recommendations,” explains Katrin Stücher. “A frequent obstacle was the weather: either it was too cold, too hot or too wet. But the side effects of the chemotherapy, such as loss of sensation, weakness, exhaustion, infections or severe diarrhea, also often meant that they had to reduce or even discontinue the program.”
For the participants in the study, the complementary exercise therapy proved valuable despite the need for occasional breaks. Muscle mass improved as did functional properties, such as balance, walking speed and leg strength. The study also showed first indications that the toxicity of the chemotherapy can be reduced through moderate activity. This is important because it is especially due to severe toxic effects that patients with gastrointestinal cancer often have to reduce the dose or even discontinue the chemotherapy altogether.
“I go walking every morning. It’s good for both my mind and my body and I’m sure it’s contributing to my recovery. I think that if you hadn’t encouraged me to continue exercising I would probably not have dared to push myself so far physically”, reported one of the participants to Katrin Stücher.
“We believe that it will make sense in future to offer patients opportunities for physical exercise during chemotherapy. To eliminate adversities through the weather, exercise rooms could be set up in hospitals. In addition, we should motivate patients to continue with the program after they have taken a break because of side effects”, says Professor Winfried Banzer, Head of the Department of Sports Medicine at Goethe University Frankfurt.
Further information: Professor Dr. Dr. Winfried Banzer, Department of Sports Medicine, Faculty of Medicine, Frankfurt University Hospital, Tel.: +49(0)69-798-24543, or Katrin Stücher, nutritionist, Katrin.Stuecher@erfolgreich-essen.de.
Household chaos makes bringing up children with ADHD more difficult
FRANKFURT. Researchers often observe inadequate parenting, a negative emotional climate and household chaos in families of children with ADHD. A research group at Goethe University Frankfurt and the universities of Bremen, Heidelberg, Tübingen and Kiel has now explored how these factors interrelate. The result is astounding.
“We assumed that the parents of children with ADHD found it difficult to maintain a structured family life and daily routines due to their children’s symptoms. In turn, household chaos has an adverse effect on emotional climate and parents’ behaviour”, explains Dr. Andrea Wirth, research associate at the Department of Educational Psychology of Goethe University Frankfurt.
The data of 84 children aged between 7 and 13 years was included in the study, of which 31 children were assigned to the ADHD group and 53 to the control group. Parental behaviour was assessed using a standardized questionnaire, which asked to what extent the parents looked after their children, praised or criticized them, how consistent they were in their parenting and whether they resorted to physical punishment. In order to document the emotional climate in the family, the psychologists asked one of the parents to talk about his or her child for five minutes and describe the child’s personality as well as his or her relationship to it. Household chaos was also recorded using a standardized test.
As expected, parenting by the parents of children with ADHD was less adequate, they criticized their children more often und reported more household chaos than the parents of the children in the control group. However and to the psychologists’ surprise, the parents of children with ADHD rated their relationship to their children more positively than the parents of children without ADHD. The researchers presume that a possible reason, amongst others, might be that some of the families involved were already undergoing therapy, since improvements in the parent-child relationship have already been proven both for interventions with medication as well as those based on behavioural therapy.
The exact relationship between the three constructs was examined with the help of statistical analyses (mediation analyses). “Household chaos seems to be some kind of mechanism through which the symptoms of children with ADHD have a negative impact on their parents’ behaviour towards them”, says Andrea Wirth. However, a chaotic environment does not appear to affect the emotional climate in the family. This contradicts earlier studies which had found a link between inadequate parenting and emotional climate. “A highly chaotic and unstructured household, to which the children’s ADHD symptoms are a contributing factor, makes it difficult for their parents to be authoritative in their upbringing. At the same time, it can be assumed that the parents - despite the prevailing chaos - are fond of their children, speak positively about them and enjoy spending time with them.”
The research group at the LOEWE centre IDeA, of which Andrea Wirth is a member, is drawing up recommendations for future research aimed at designing parent training which can help parents to plan family life better, establish fixed routines and rituals, and organize daily life more efficiently. These may include, for example, turning off the radio and the television when the child is doing its homework, leaving the room to make phone calls, only receiving guests at certain times and letting the child do its homework alone in a quiet room.
Wirth, A., Reinelt, T., Gawrilow, C., Schwenck, C., Freitag, C. M. & Rauch, W. A. (2017). Examining the relationship between children’s ADHD symptomatology and inadequate parenting: The role of household chaos. Journal of Attention Disorders. Advance online publication. doi:10.1177/1087054717692881
Further information: Dr. Andrea Wirth, Department of Educational Psychology, Faculty of Psychology and Sports Sciences, Westend Campus, Tel.: +49(0)69-798-35398, firstname.lastname@example.org.
Next exhibition at Goethe University’s Giersch Museum opens on March 19th
The 1950s represented an era of new beginnings. Abstraction dominated the art of the young Federal Republic of Germany. Featuring 74 works by 20 artists, Giersch Museum’s new exhibition is a tribute to the artistic diversity of that decade.
Organic and vegetal, rigorously geometrical, impulse and gesture-oriented or tentatively scriptural; bursting with colour, subdued in tone, even monochrome – the abstract art of the period was vastly heterogeneous in terms of form and colour alike. Yet the dissolving boundaries also granted new freedom in the definition of the painting as such and its various genres.
The exhibition at Goethe University’s Giersch Museum starts with the Darmstädter Gespräch (Darmstadt Dialogue) of 1950, which served to take stock of post-war contemporary art and its conflict between figuration and abstraction. The focus is on the most important artists’ groups of the time – “junger westen” in Recklinghausen, “ZEN 49” in Munich and “Quadriga” in Frankfurt – with their wide-ranging origins, venues and protagonists. Works by painters Gerhard Hoehme, Emil Schumacher and Heinrich Siepmann and the sculptor Ernst Hermanns testify to the new paths explored by the “junger westen” (“young west”). Rupprecht Geiger, K. R. H. Sonderborg, Fritz Winter and the sculptress Brigitte Meier-Denninghoff stand for the Munich group “ZEN 49”. The exhibition pays special attention to the painters of the Frankfurt “Quadriga” – K. O. Götz, Otto Greis, Heinz Kreutz and Bernard Schultze: a representative selection of their works from the 1950s sheds light on the four artists’ individual paths. Finally, with examples by Hermann Goepfert, Hans Haacke, Peter Roehr and Franz Erhard Walther, a look at Kassel’s documenta II of 1959 and the emerging generation of artists marks the transition to the 1960s, the age of the “ZERO” movement and object art.
Goethe University’s Giersch Museum perceives itself as the “university’s window” on the city of Frankfurt and the Rhine-Main region. For many years, the museum has been dedicated to the research and mediation of regional art – which is unique within Frankfurt’s rich museum landscape.
This profile will remain and at the same time a particular aspect will become more important: the museum as a location for exhibitions that show important elements of scientific and intellectual life at Goethe University and which allows suitable topics and exhibits to be presented to a wider audience.
Freedom at Last: Abstraction in the 1950s
Exhibition at Goethe University's GIERSCH MUSEUM
March 19th 2017 – July 9th 2017
Private guided tours in English (1 hour) by arrangement: +49(0)69-13821–010
Price on weekdays € 75 (plus admission)
Price on Saturdays, Sundays and holidays: € 80 (plus admission)
Schaumainkai 83 (Museumsufer)
60596 Frankfurt am Main
Witnessing the birth of a tiny RNA at brain synapses
Proteins are the building blocks of all cells. They are made from messenger RNA (mRNA) molecules, which are copied from DNA in the nuclei of cells. All cells, including brain cells, called neurons, carry out their functions by carefully regulating the amount and kind of proteins they make. An important feature of neurons is their ability to communicate with one another at synapses, the points of contact between two cells. Synapses use proteins that are synthesized close-by to fuel communication and the formation of memories.
In neurons and other cells, protein synthesis is regulated by microRNAs, very small “non-coding” RNAs that bind, using complementary sequences, to mRNA and prevent the mRNA from being made into protein. microRNAs are made from larger precursor RNA molecules by several processing steps in the nucleus and cytoplasm. In individual cells, copy numbers of most microRNAs in single cells are relatively low in contrast to potential mRNA targets within individual cells where copy numbers can be up to 10,000 molecules. As such, the absolute number of potential mRNA targets within a cell for a single microRNA species could be very high (e.g. millions), raising the question of how a microRNA can effectively regulate a particular target mRNA.
In the February 10th issue of Science, the Schuman and Heckel labs, from the Max Planck Institute for Brain Research and Goethe University, respectively, show that neurons have solved the abundance problem by moving the site of microRNA maturation (or “birth”) away from the cytoplasm out to the dendrites, thin processes, which are closer to where synapses are. This puts the newly born microRNA into much smaller environment with fewer mRNA target options.
“We tested this hypothesis by using a clever design of a fluorescent molecular reporter, modelled after an immature microRNA”, Heckel says. “We filled neurons with this probe and then stimulated individual synapses. To our surprise, we could then see bright fluorescent spots at the stimulated synapses, showing us the birth of the microRNA. We then saw that the microRNA target was downregulated in the neighborhood of the dendrite where the microRNA was born”.
Schuman: “By moving the birthplace of the microRNA to the dendrites and synapses where it is closer to its targets, neurons have solved the microRNA-mRNA numbers game and gained a way for external events-resulting in the activation of synapses, to control the local expression of important brain molecules which is important for neuronal communication and also for memory formation”.
Publication: Sambandan, S., Akbalik, G., Kochen, L., Rinne, J. Kahlstatt, J., Glock, C. Tushev, G., Alvarez-Castelao, B., Heckel, A. and Schuman, E.M. (2017). Activity-dependent spatially-localized miRNA maturation in neuronal dendrites. Science 355: 634-637 Contact: Prof. Dr. Erin M. Schuman, Max Planck Institute for Brain Research, Max-von-Laue Str. 4, 60438 Frankfurt am Main, Germany, Email: email@example.com, T: +49 69 850033 1001 (Ms. Nicole Thomsen).