Paul Ehrlich and Ludwig Darmstaedter Prize 2017 awarded to Pitt Cancer Researchers
Scientists looking for new tumor viruses have to keep an eye out for the virus genes rather than the viral particles. This year's winners of the Paul Ehrlich and Ludwig Darmstaedter Prize were twice successful with this strategy.
FRANKFURT am MAIN. Two Americans, Yuan Chang and Patrick S. Moore, will receive the 2017 Paul Ehrlich and Ludwig Darmstaedter Prize today in Frankfurt's Paulskirche for their discovery of the tumor viruses HHV-8 and MCV by means of a clever subtraction strategy. HHV-8 is the human herpesvirus 8, and MCV stands for Merkel cell polyomavirus. "With their decision to search for the viral genes rather than the viral particles, the prizewinners have taken a major step forward in the hunt for new human tumor viruses and have laid the foundation for further discoveries. The discovery of further human tumor viruses in future remains a distinct possibility," wrote the Scientific Council in substantiating its decision. One in every six cancers in the world is related to a viral infection However, the risk of cancer from a viral infection is lower in the Western industrial countries than in the developing world. Yuan Chang is Professor of Pathology at the University of Pittsburgh Cancer Institute. Patrick Moore is Professor and Director of the Cancer Virology Program at the University of Pittsburgh Cancer Institute. They are a wife and husband team.
HHV-8 causes Kaposi's sarcoma, a tumor of the blood vessel cells, which can be seen on the skin with the naked eye owing to its pronounced red or purplish spots. The tumor occurs mainly in AIDS patients. In their search for HHV-8, Chang and Moore subtracted the entire human genome from the genomic DNA of the tumor cells. The idea behind this approach was that the remaining sequences would, in the best case, belong to the tumor virus and not to the human genome. Following this strategy, the prizewinners isolated two small DNA fragments that they were eventually able to assign to a new herpesvirus. When they published their findings in 1994, they named the virus Kaposi's sarcoma-associated herpesvirus (KSHV). It was later given the official name HHV-8.
MCV is responsible for causing Merkel cell carcinoma, an extremely rare, malignant skin cancer. Chang and Moore refined their strategy in the search for the virus causing Merkel cell carcinoma. Fourteen years after the discovery of HHV-8, their approach was no longer to subtract the entire human genome from the tumor DNA but only the RNA sequences, thereby greatly simplifying the search. In addition, the sequences were not subtracted in a laboratory experiment but computationally, for which they used the published human genome sequences.
Chang and Moore not only discovered the viruses but also showed that they are in fact responsible for the two types of cancer. All Kaposi's sarcomas everywhere in the world contain HHV-8, in other words, not only those that occur in the context of AIDS but also the rare sarcomas that occur sporadically in the USA, Europe and Africa. The infection also precedes the tumor development. It was more difficult to demonstrate that MCV is the culprit in Merkel cell carcinoma because the virus is present in humans' normal skin flora. Chang and Moore showed that in all cells of a givenMerkel cell carcinoma the virus is located at the same site in the genome – although the sites will differ between different Merkel cell carcinoma patients. The tumor must therefore have developed from a single cell with integrated MCV, and this fact, along with further findings, confirmed its causal role.
If some tumor viruses are ubiquitous, why does not everyone fall ill? The tumor viruses first have to overcome the cell's defenses – either by means of cancer genes that they bring with them as with HHV-8 or through mutations as with MCV – and the immune system has to be weakened for cancer to actually develop. Is there a vaccine or treatment for HHV-8 or MCV? "The situation with Kaposi's sarcoma is disappointing for us," says Moore. "Although the community of researchers has found candidates for a vaccine and target molecules for therapy, there is little commercial interest in developing a vaccine or a specific drug therapy." Chang adds: "For Merkel cell carcinoma, however, we're optimistic. Many patients respond to checkpoint inhibitors, some even go into complete remission." Checkpoint inhibition is a promising new therapeutic principle in cancer treatment.
The €120,000 Paul Ehrlich and Ludwig Darmstaedter Prize is among the most prestigious international awards granted in the Federal Republic of Germany in the field of medicine. The Prize will be presented by Professor Harald zur Hausen, Chairman of the Scientific Council.
Short biography of Prof. Yuan Chang
Yuan Chang (57 years of age) is a virologist and pathologist. She was born in Taiwan and grew up in Salt Lake City. She studied medicine at the University of Utah and holds a Bachelor of Science degree from Stanford University. Chang worked at Stanford University Medical Center, at the DNAX Research Institute of Molecular Biology in Palo Alto, and at Columbia University`s College of Physicians and Surgeons in New York, before moving to the University of Pittsburgh in 2002. She is currently American Cancer Society Research Professor, Distinguished Professor of Pathology, and UPMC Endowed Chair in Cancer Virology at the University of Pittsburgh School of Medicine. Yuan Chang has won numerous awards. This year she will receive the 2017 Passano Foundation Award together with her husband Patrick Moore.
Short biography of Prof. Patrick S. Moore
Patrick S. Moore (60 years of age) is an epidemiologist and virologist. He studied biology at Westminster College in Salt Lake City and completed his master's degree in chemistry at Stanford University. He studied medicine at the University of Utah and obtained a Master of Public Health at the University of California, Berkeley. He worked in Ghana in 1985 and then in Liberia in 1986. He then joined the Centers for Disease Control and Prevention, where he was involved in international public health interventions in Chad, Ethiopia, Saipan, Nigeria, Nepal and Somalia. He worked for a short time as Deputy Commissioner of the New York City Department of Health in 1993 before moving with his wife to Columbia University in New York. Moore was Professor of Public Health Division of Epidemiology at Columbia University until 2002, when he took up a position at the University of Pittsburgh. He is the Director of the Cancer Virology Program at the University of Pittsburgh Cancer Institute, American Cancer Society Research Professor, Distinguished Professor of Microbiology and Molecular Genetics and the Pittsburgh Foundation Chair in Innovative Cancer Research at the University of Pittsburgh School of Medicine. Patrick S. Moore has won numerous awards.
The Paul Ehrlich and Ludwig Darmstaedter Prize
The Paul Ehrlich and Ludwig Darmstaedter Prize is traditionally awarded on Paul Ehrlich's birthday, March 14, in the Paulskirche, Frankfurt. It honors scientists who have made significant contributions in Paul Ehrlich's field of research, in particular immunology, cancer research, microbiology, and chemotherapy. The Prize, which has been awarded since 1952, is financed by the German Federal Ministry of Health, the German association of research-based pharmaceutical company vfa e.V. and specially earmarked donations from companies. The prizewinner is selected by the Scientific Council of the Paul Ehrlich Foundation.
The Paul Ehrlich Foundation
The Paul Ehrlich Foundation is a legally dependent foundation which is managed in a fiduciary capacity by the Association of Friends and Sponsors of the Goethe University, Frankfurt. The Honorary Chairman of the Foundation, which was established by Hedwig Ehrlich in 1929, is the German Federal President, who also appoints the elected members of the Scientific Council and the Board of Trustees. The Chairman of the Scientific Council is Professor Harald zur Hausen, and the Chair of the Board of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of the Board of Trustees.
You can obtain selected publications, the list of publications and a photograph of the laureates from the Press Office of the Paul Ehrlich Foundation, c/o Dr. Hildegard Kaulen, phone: +49 (0)6122/52718, email: email@example.com and at www.paul-ehrlich-stiftung.de
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