EditorialRubrik 3

Tradition and innovation— microbiology in Jena

For science in Germany, 2018 will be biology and Experimental Therapy a year of important decisions in the (ZIMET), led by Hans Knöll, gave rise Excellence Strategy programme of the to today’s Leibniz Institute for Natu- German federal government and feder- ral Product Research and Infection al states. A total of 195 draft proposals Biology – Hans Knöll Institute (HKI). for Clusters of Excellence have been The University benefits greatly from Prof. Dr Thorsten Heinzel submitted in this national competition. its close cooperation with the HKI and Vice-President for Research at Friedrich Schiller Of the 88 drafts that will be developed other non-university research institu- University Jena into full proposals by February, two tes of the Leibniz Association, the Max are from Friedrich Schiller University, Planck Society, the Fraunhofer Society, Jena (FSU). From 2019, between 45 and and the Helmholtz Association, in par- 50 Clusters of Excellence will be fund- ticular in preparing the »Microverse«

PUBLISHER: Central Communications/Press Office on be- ed with 385 million euros per year. Cluster proposal. half of the President of the Friedrich Schiller University Jena EDITORIAL AND DESIGN: Dr Ute Schönfelder, Juliane The Cluster proposal »Enlightening The Cluster combines the expertise Dölitzsch, Stephan Laudien, Axel Burchardt (responsible the Receptome« is a joint application of the FSU’s profile lines LIGHT and under German press legislation), Liana Franke, Kai Friedrich, of FSU and the University of Würz- LIFE, and builds on the very success- Monika Paschwitz (editorial assistant) and Kerstin Apel (secretariat) burg. Its key objective is systemati- ful Excellence Graduate School »Jena GRAPHIC DESIGN: Timespin—Digital Communication cally to unravel the »receptome«—the School for Microbial Communica- GmbH, Sophienstraße 1, D-07743 Jena sum of all receptor molecules of an tion« (JSMC), which was set up in 2007. ADDRESS: Friedrich Schiller University Jena organism—and make use of it in treat- Based on strategic cooperation bet- Fürstengraben 1, D-07743 Jena ing diseases (see p. 49). The Cluster ween participating institutes, several Phone: ++49 3641/9-31040, Fax: ++49 3641/9-31032, Email: [email protected] proposal »Balance of the Microverse« large third-party funded projects such OVERALL PRODUCTION: Druckhaus Gera GmbH, Ja- focuses on microorganisms and their as Collaborative Research Centres cob-A.-Morand-Straße 16, D-07552 Gera interactions with other microorgan- have been successfully established. TRANSLATION: Michelle Wilbraham, Jernej Biščak isms, and with their environment—the Obtaining funding for the Microverse INTERNET: www.uni-jena.de/en/lichtgedanken »Microverse«. and the Receptome Clusters would re- ISSN: 2510-3849 PUBLICATION DATE: March 2018 present a continuation of this positive PHOTOS: Kasper (1, 3, 5, 6, 7, 8, 11—14, 16, 19, 25—29, 33, The diversity of these »microworlds« is development and enhance the interna- 35, 40, 42, 43, 44, 45, 46, 48, 51, 56—61, 63, 64, 66), Günther the focus (see p. 8—46) of the present tional visibility of the FSU. (5, 18, 23, 55, 63, 35, 68), Frenzel (5, 71, 73), Beutel (5, 52), issue of LICHTGEDANKEN. Current Lehmann (5, 36, 37, 38), Fischer (10), Döring (5, 20, 24), Beemelmanns (30, 32), Rischer (31), Mittag (34), Gutmann FSU research topics in microbiology I hope that you enjoy reading this issue (39), Kirtzel (43), Archiv (47), Schroll (48), Yan (50), Stein concern vital issues for the future, of LICHTGEDANKEN. (53, 54), Hoffmeister (64), Alivernini (70, 72), Biehl (72, 73), such as fighting infectious diseases, privat (74). sustainably securing our basic needs, Reproduction only permitted with approval. No liability is assumed for spontaneously submitted manuscripts, photos as well as ensuring a stable climate.

or similar material. Articles carrying the name of the author do not necessarily reflect the views of the publisher or With these topics, the University is the editorial team. The signatories are responsible for the continuing the long tradition of micro- content. In some places we have only used the male form in biology in Jena, initiated by Hans articles to improve their readability. The formulations chosen denote men and women in equal measure. Knöll in the 1940s when he first started the industrial production of penicillin here. The Central Institute for Micro- Jena, January 2018

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FEATURE MICROSCOPIC WORLDS

08 TINY ORGANISMS OF GREAT SIGNIFICANCE How microbial communities function in the natural world; how host organisms and the environment benefit from them; and how communication works in the diverse microbiomes: these are all topics currently being studied by FSU researchers, together with numerous partners.

14 MICROSCOPIC FRIENDS AND HELPERS Microbiologist Prof. Axel Brakhage discusses in an interview what makes micro- organisms so successful and what human beings can learn from them.

18 MICROORGANISMS AND HEALTH How harmless residents of the gut can turn into dangerous intruders; why advances in modern medicine can become a health risk; the possible psychological conse- quences of a life-threatening sepsis; and how resistant bacteria can be detected quickly and accurately.

26 DROPS OF BLOOD IN FOCUS In the research project »BLOODi«, scientists are working on developing a dynamic haemogram. The report follows the research team and shows how new optical technologies can be used to identify infections in whole blood.

30 MICROORGANISMS AND THE ENVIRONMENT How termites cultivate fungi to use them as food and bacteria hunt down green algae; how microorganisms survive in groundwater and rock, and contribute towards biomineralisation.

44 IMAGING WITH »X-RAY VISION« With ultrashort X-ray pulses, processes and structures can be resolved to the nanometre range.

46 GPS FOR ANTIBIOTICS Using polymer-based nanosystems, drugs could in future be precisely directed to the source of an infection. Contents 5

18 IMMUNOLOGY 24 PHOTONICS 37 ECOLOGY FROM HARMLESS FUNGUS RAPID TEST FOR SURVIVAL SPECIALISTS TO DEADLY THREAT ANTIBIOTIC RESISTANCE IN THE UNDERWORLD

50 3D RECONSTRUCTION 68 PORTRAIT 70 EXPEDITION BEETLE FOSSIL CHRISTOPH REDIES— »GEO« MAGAZINE SENDS BROUGHT BACK TO LIFE ANATOMIST AND ARTIST RESEARCHER TO AFRICA

NEWS PROJECTS TICKER 06 The latest from town and gown 58 Excavating traces of ancient 63 Research in brief earthquakes

CALENDAR 59 Securing, using and sharing WISSENSCHAFTSFOTO 47 Myth of the October Revolution 60 Preventing terrorism 66 More safety—more risk?

61 The best of both nano worlds

TOPICS 62 Haussknecht’s oriental souvenirs PORTRAIT 48 Surviving with leukaemia 68 The art of science and science of art 50 »Bad Boy« of the beetles REFLECTION 53 Gifts to the gods 52 Outliving life itself BEHIND THE SCENES 56 JUMP: to attract—or not attract 74 Research in microgravity

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the Universities of Jena, Halle and Leip­ zig, and is being supported by around 2.7 million euros in funding from the Federal Ministry of Education and Re- search (BMBF). »Our aim is to develop nutritional plans or concepts for healthy people with various different dietary habits, which ensure an adequate intake of all essen- tial nutrients,« explains Dr Christine Biomarkers for healthy food Dawczynski, who leads the new junior research group. In order to give nutrition-related stu- Junior research group »Nutritional Concepts« is developing plans for dies greater and lasting value, the group different dietary types and has received federal government funding of focuses on identifying and validating some 2.7 million euros biomarkers that reliably reflect specific nutritional patterns and thus reveal con- nections between the intake of nutrients Vegetarian, vegan, flexitarian—people to change this. Over the next five years, and an individual’s state of health. nowadays follow many different diets. the junior research group »Nutritional Scientists can already detect omega-3 However, anyone who shuns particular Concepts« aims to develop specific nu- fatty acids of marine origin in the blood, foods runs the risk of suffering from a tritional plans for a variety of diets. These for example, and the objective of the ju- deficiency in important nutrients. Al- concepts will be validated by human in- nior research group is to establish and though there is plenty of advice availa- tervention studies. validate biomarkers that reflect, for ble regarding various diets, for most The group is integrated within the Com- example, the consumption of cereals, approaches a valid scientific database petence Cluster for Nutrition and Car- meat, dairy products, chocolate, fast is missing. Nutritionists in Jena want diovascular Research (nutriCARD) of food or fruit, and vegetables. sh

Healing chronic wounds

Research group »InflammAging« aims to achieve better wound healing using nanocellulose—700,000 euros funding by the federal state

The interdisciplinary research group order to treat chronic inflamed wounds »InflammAging« at the University of more effectively. Jena has being funded for three years In Germany, some 400,000 people a year by the Free State of Thuringia with develop a form of decubitus that requi- 700,000 euros from the European Soci- res treatment. Decubitus ulcers, also cal- al Fund. The research consortium aims led bedsores or pressure sores, occur in to develop new therapeutic approaches response to damage to the skin and the for treating chronic wounds—especial- underlying tissue that can develop into ly for older people. The team, bringing a »silent« inflammation. »Anti-inflam- together researchers from pharmacy, matory strategies for the prevention and nutrition sciences and medicine, is treatment of such inflammatory condi- pursuing its aim using a combination tions are therefore an important field of bioactive natural products and an of research,« explains the coordinator innovative carrier material made from of the new research group, Prof. Stefan bacterial nanocellulose. The idea is to Lorkowski. Wounds are treated using Researchers aim to pack anti-inflammatory develop innovative wound dressings bioactive natural products, such as tri- molecules into wound dressings made from based on this material—created nanocellulose to treat chronic wounds more terpene acids from frankincense, which through biotechnology research—in effectively. are anti-inflammatory. AB RubrikNews 7

Two research proposals reach the final

The University of Jena has been asked to submit two full proposals for research clusters as part of the Excellence Strategy programme of the German federal and state governments. The proposals »Balance of the Microverse« and »Enlightening the Receptome: From Biophysics to Clinical Applications« have to be submitted by 21 February.

The Friedrich Schiller University sive picture of these interactions, Jena is »Enlightening the Receptome: From Jena (FSU) is enjoying success with pooling its expertise, with cooperation Biophysics to Clinical Applications« the Excellence Strategy and has between microbiology and environ- entered the final round of the com- mental microbiology, infection biology, The proposal »Enlightening the Recep- petition with two proposals for Clus- chemical biology, bio-geo-interactions, tome: From Biophysics to Clinical ters of Excellence. The proposals, systems biology, optics/photonics, ma- Application« aims systematically to one of which is a joint proposal with terial sciences, and further disciplines. unravel the »receptome«—the sum of Würzburg, cover the areas of life Apart from making technological pro- all receptor molecules of an organism sciences and natural sciences. From gress in the laboratory, the researchers —and harness it to treat diseases. The 2019, the Clusters of Excellence will anticipate finding many possible appli- Cluster proposal has been submitted by be funded with 385 million euros per cations for the benefit of people and the universities of Würzburg and Jena, year. The decisions on funding will the environment. Under the auspices and their university hospitals. Research be made in September 2018. of the FSU, the Cluster also involves groups from the Leibniz Institute for Jena University Hospital; the Leibniz Age Research – Fritz Lipmann Institute Institute for Natural Product Research and the Max Planck Institute for Chemi- »Balance of the Microverse« and Infection Biology—Hans Knöll In- cal Ecology are also involved. Speakers stitute (HKI); the Fraunhofer Institute are Prof. Markus Sauer from Würzburg, The aim of the Cluster »Balance of for Applied Optics and Precision En- and Prof. Klaus Benndorf and Prof. the Microverse«, whose speaker is gineering (IOF); the Leibniz Institute of Christian Hübner, both from Jena Uni- Prof. Axel Brakhage, is to study mi­ Photonic Technology (IPHT); the Max versity Hospital. With this Cluster, the croorganisms and their interactions Planck Institutes for Chemical Ecology, scientists want to continue to build on with other microorganisms, as well Biogeochemistry and the Science of Hu- their successful collaboration in the Col- as their environment—the Microver- man History; the Helmholtz Institute, laborative Research Centre »Receptor- se. In order to build up a comprehen- Jena; and DLR Institute of Data Science Light«. AB

New driver of innovation

A new Innovation Center for Quantum Optics and Sensor Technology (InQuoSens) is being created in Thuringia

The new centre is being funded with 1.5 million euros from the European Union and the same amount from the Free State of Thuringia. The Friedrich Schiller University (FSU) in Jena and the Technical University of Ilmenau (TU Ilmenau) will share responsibility for the dual-site innovation centre. »With InQuoSens, an effective research consortium has been created, which is active in a field that continues to be the subject of excellent basic research, but has also already been driving real Presentation of the funding awards (from left): Andreas Tünnermann (Fraunhofer innovations in optical sensors,« said the FSU’s President Prof. Institute for Applied Optics and Precision Engineering and FSU), Walter Rosenthal Walter Rosenthal at the presentation of the funding awards at (FSU), Wolfgang Tiefensee (Thuringian Ministry of Economy, Science and Digital the end of October 2017. Society), Kai-Uwe Sattler and Jens Müller (TU Ilmenau).

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Fungus cultures in the »Jena Microbial Resource Collection« (JMRC), a shared facility of the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI) and Friedrich Schiller University. The JMRC curates a collection of around 50,000 microorganisms for research purposes. SCHWERPUNKT 9

FEATURE Microscopic worlds

Tiny organisms of great significance

Microorganisms are secretly the rulers of the world: not only have they colo- nized virtually every spot on Earth—all higher organisms, whether plants, ani- mals or humans, have communities of microbes living on them. Innumerable processes of life and abiotic processes such as the climate are influenced by interactions with complex microbial communities. These diverse microscopic worlds have long been the subject of intensive research in Jena, at the Universi- ty and Jena University Hospital, as well as at non-university research institutes such as the Leibniz Institute for Natural Product Research and Infection Biolo- gy – Hans Knöll Institute (HKI). »

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Einführender Text Mikrobielles Leben Mikrokosmos, Mikrobielle Kommunikation etc Between minimalism and diversity

They are specialists in survival and transformation, talented communicators and usually part of huge communities. Their flexibility, diversity and vast numbers are unsurpassed. Microorganisms represent a good two-thirds of all the biomass on Earth. How their communities function in the natural world, how they create and maintain conditions of dynamic equilibrium with host orga­ nisms and with their environment, and how communication is achieved in the various micro- biomes—these are all topics that scientists in Jena are studying in a number of interdisciplinary research consortia.

BY UTE SCHÖNFELDER

Huge numbers of microbes are present in fresh water —in rivers and lakes, for example—but also in the salt water of seas and oceans. They are essential to the chemical processes in water bodies. SCHWERPUNKT 11

Microorganisms consist of just a single Microbiological research at the Friedrich Schiller University Jena cell or aggregates of single cells. These and non-university institutions in the region microscopic organisms include bacteria, archaea, most fungi (including yeasts), microalgae, and protozoa (amoeba). The Graduate School »Jena School for Microbial Communication« (JSMC), founded Viruses, which are not actually living at the University in 2006, has been funded within the Excellence Initiative of the fe- organisms, are also usually counted deral and state governments since 2007. The school brings together scientists from among the microorganisms. Microbial the natural and life sciences, for example biology, chemistry, medicine, pharmacy, life is very limited, reduced to the bare biotechnology, geology, physics, and informatics. The JSMC’s key objective is to deci- minimum. However, despite their mini- pher the »language« that microorganisms communicate with each other and higher malistic structure, microorganisms have organisms, and with the environment. This is a prerequisite for a better understan- a wide diversity of metabolic paths and ding of many diseases or the causes of environmental damage. Many findings from products at their proposal, which makes basic research form the basis for developing innovative technologies and new active them extremely adaptable. substances. Since the school’s foundation, more than 130 doctoral candidates have obtained their doctorate. The JSMC currently has 135 active doctoral candidates, of whom one in three come from abroad. Virtually every habitat on Earth is colonized by microorganisms The Collaborative Research Centre/Transregio »FungiNet« is working on pathogenic fungi. In the research consortium launched in 2013, scientists from the University, At a rough estimate, there are around Jena University Hospital and the Leibniz Institute for Natural Product Research and 1030 microorganisms on Earth—1 follo- Infection Biology—Hans Knöll Institute (HKI) are collaborating with colleagues from wed by 30 zeros—and the majority of the University of Würzburg and its university hospital to gain a better understanding them are as yet undiscovered. Accor- of life-threatening infections caused by fungi and develop new therapies to tackle ding to estimates, we know only one infections. to five per cent of all microorganisms. What is clear, however, is the huge sig- Also since 2013, ecologists, geoscientists and chemists have been working in the nificance of these minute organisms for Collaborative Research Centre »AquaDiva« to analyse the links between the habitats life on Earth. Microbes play a decisive of plants and microorganisms above and below ground, as well as the processes role in material cycles in nature and thus that take place in those habitats. The aim is to use the knowledge gained to make ensure the essentials of life for all higher recommendations for sustainably protecting these ecosystems and the services organisms. they provide to humans. This specifically concerns protecting the natural ground- water reservoirs, among other things. Apart from the scientists from the University, »AquaDiva« also includes researchers from the Max Planck Institute for Biogeoche- Water as habitat mistry, the Leibniz Institute of Photonic Technology (IPHT) and the Helmholtz Centre for Environmental Research (UFZ). Whether a puddle, garden pond, ri- ver or an ocean, all bodies of water are Chemical mediators—signal molecules that determine the interactions between cells swarming with microorganisms—from and organisms of one or more species—have been the focus of the Collaborative Re- bacteria and algae, through parameci- search Centre »ChemBioSys« since 2014. In this work, researchers from the Universi- um and ciliates, to amoeba. It was the ty of Jena, the HKI and the Max Planck Institute for Chemical Ecology are listening to Dutch naturalist and cloth merchant, —and deciphering—the chemical »babble« of these signals in biosystems that inclu- Antoni van Leeuwenhoek, who first de fungi, bacteria, microalgae, plants, animals, and human cells in order to clarify how discovered and described the microbial such community structures arise and function, and how their diversity is maintained. life that he found in a pool of water in the 17th century. In the Collaborative Research Centre (CRC) »PolyTarget«, which started in 2017, re- Algae are responsible for around half of searchers from many disciplines aim to develop nanoparticles with which drugs to all the oxygen produced on the planet treat microbial infections can be steered precisely to where they are required. This and also bind the greenhouse gas car- CRC brings together chemists, materials scientists, pharmacists, medical experts, bon dioxide. They are therefore a key and biochemists of the University and the University Hospital, as well as scientists primary producer in the food chains of from the IPHT, the HKI and the Leibniz Institute on Aging (FLI). This initiative further lakes and seas. At the University Jena, strengthens the already strongly positioned research in Jena on sepsis and infection.

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biologists and chemists are studying the interactions between the freshwater alga Chlamydomonas reinhardtii (see p. 33) and various bacteria, among other things. Researchers at the Institute of Inorganic and Analytical Chemistry are focusing on marine diatoms and studying the influence of chemical signal molecules on their way of life, reproduction or susceptibility to viruses. Geoscientists and ecologists are also on the trail of microbial life in groundwater (see p. 36).

Humans as habitat

Microorganisms not only colonize every habitat on Earth, but also live on, and in equilibrium with, virtually every higher organism, including humans. We are all walking »ecosystems«. Every one of us carries about a kilo of microbial biomass on and in our bodies (see interview p. 14). The intestines in particular are colo- nized by several hundred species of bac- teria, archaea and fungi, with comple- tely individual compositions in every organism. The microbes living inside us help with our digestion, breaking down indigestible food for us, for example. They also support our immune system, produce vitamin K, which is essential for blood coagulation, and break down harmful substances. Research groups in Jena are looking at the pathogenesis of systemic fungal infections (see p. 18), identifying and characterising novel active substances from nature for the treatment of infec- tions (see p. 30) and developing, in in- terdisciplinary research consortia, new methods of diagnosing and treating se- rious infectious diseases which can lead to sepsis (see p. 20 and p. 24). SCHWERPUNKT 13

Soil and rock as habitat

There is a wide diversity of microbial life not only in habitats on the surfa- ce, but also—and especially—under­ ground. Researchers assume that one third to one half of all the biomass on our planet is produced below ground— by microorganisms. Whether in woods, fields or in your gar- den at home: the soil is teeming with a wide variety of life forms. Soil bacteria and fungi live mainly among the roots of plants in the soil. There, they help make organic material decompose, pro- vide nutrients and break down harmful substances. However, microorganisms are also at home in layers of rock deep under- ground. Some bacteria and archaea are capable of living at depths of several ki- lometres, at extreme temperatures and under high pressure. They need neither organic material nor light in order to survive, but use inorganic rock to gener- ate energy. These organisms have very slow metabolism and it is estimated that some divide only once every 1,000 years. In current research projects, microbiolo- gists of the University of Jena are study- ing, for example, how fungi break down rock and how bacteria form mine- rals (see p. 40). Geoscientists and ecolo- gists are seeking out hitherto unknown microbes in rocks in Thuringia’s Hai- nich National Park and in the Thuringi- an Basin (see p. 36).

Microbes living in the soil break down dead wood and other plants, and turn them into valuable humus.

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Microscopic friends and helpers

In view of growing threats from global infectious diseases, multiresistant bacteria and dwindling numbers of effective drugs, microorganisms and fungi do not enjoy the best of reputations. However, these threats to our health, which must undoubtedly be taken seriously, can easily blind us to the huge significance of microbes in maintaining human health, an intact environment and a stable climate. In an interview, Jena microbiolo- gist Prof. Axel Brakhage discusses what makes microorganisms so successful and what we can learn from them.

INTERVIEW: UTE SCHÖNFELDER

Prof. Axel Brakhage is Professor of Microbiology Microorganisms are present virtual- nuclear radiation. This enables them in and Molecular Biology at the University of Jena ly everywhere: in the soil, the water principle to colonize all parts of the pla- and director of the Leibniz Institute for Natural and the air. How do bacteria, fungi or net and, of course, all higher organisms. Product Research and Infection Biology – Hans Knöll Institute (HKI). He coordinates the Excel- microalgae manage to colonize just Plants, animals and humans provide lence Initiative Graduate School »Jena School about every habitat on Earth? habitats for a huge number and diversi- for Microbial Communication« (JSMC) and is, A key characteristic of microorganisms ty of microorganisms. Every one of us among other things, speaker of the Collaborative is their metabolic diversity. They have at carries a kilo or so of bacteria in our in- Research Centre/Transregio »FungiNet« (see box their disposal an improbably large num- testines, in our mouths and on our skin. p. 11) and of the research consortium »Infect- Control 2020«. ber of metabolic pathways—more than any higher organism. This makes them Can we therefore consider diversity to very flexible, so that they can adapt ra- be the microbial recipe for success? pidly to any environmental conditions, Without a doubt. But there is a second even those that are very extreme, such important factor for success, which is as temperatures over 100 degrees Cel- their abundance. There are just so many sius, absolute aridity, high pressure or microorganisms! Their numbers exceed SCHWERPUNKTFEATURE 15

those of all other organisms in the world. multitude of processes that affect our people a year die of infectious disea- As a result, the number of microbial ge- state of health and our well-being. If the ses, an estimated 30,000 of them due to nes also far exceeds that of the higher flora is not in equilibrium, we become multiresistant microorganisms. This is organisms. They reproduce quickly and ill. There are millions of people who suf- a ticking time bomb. We are in a race their genetic material is highly dynamic. fer from chronic bowel inflammation, against time, as new pathogens are de- Various different species of bacteria are for example, because their microflora is veloping means of resistance, and that able to exchange genes with one an- not in equilibrium. If we knew how to significantly faster than we can develop other, through what is known as hori- influence this flora—which microorga- new active substances—new antibiotics. zontal gene transfer. This creates a large nisms we should encourage and which It is true that throughout human histo- gene pool, which enables rapid changes ones we should inhibit—this would ry there have been epidemics caused in the genomes of various species. bring great relief to these patients. by microorganisms, which have depo- In addition, there are challenges that af- pulated whole areas. However, today What can we then learn from this ex- fect the whole of humanity, or even the the risk is much higher that infectious tremely successful microscopic world? entirety of life on Earth, such as climate diseases could develop into pandemics, From microorganisms we can learn, change. A major problem in this context spreading extremely quickly across for example, how to break down harm- is the greenhouse gas methane, which national borders and between conti- ful substances in the environment or is many times more potent than car- nents. With air travel, pathogens can go how to make use of microbial metabo- bon dioxide. And methane is generated around the world in 36 hours. lic pathways in biotechnology. We can exclusively by microorganisms that live learn from them how to make natural in the stomachs of ruminants or in the What are the most dangerous patho- products—active substances—to treat soil. If we managed to manipulate the gens that currently represent a threat diseases, for instance. Above all, howe- hordes of microbes currently producing to human health? ver, it is important for us to learn how huge amounts of methane, in such a These definitely include multiresistant microorganisms manage to communi- way that methane production was stop- strains of bacteria—of Klebsiella pneumo- cate with each other and with their en- ped or at least reduced, we would have niae or Pseudomonas aeruginosa, for ex- vironment, and how they succeed in one less climate problem. ample—against which there is no longer maintaining their communities in a dy- any effective antibiotic. These bacteria namic equilibrium. can trigger life-threatening lung diseas- es, especially in people with a weak- Why is that important? ened immune system. There are also Take human beings as an example. We Microorganisms have formed other multiresistant bacteria, and we live with around the same number of and changed us in the course of are simply no longer able to treat such microorganisms as our body has cells. our joint evolution. infections. There are additionally a few The question here is how do these human-pathogenic fungi, such as yeast microorganisms manage to live in such fungi or moulds, which cause invasive harmony with us that we provide them infections and against which there are with a suitable habitat and they do not as yet no effective drugs or treatment make us ill? They have learnt this over strategies. the course of evolution: they »com- It is not only scientists like you and Recent data suggest that an intact municate« with each other and with our your colleagues from universities and microbiome helps to boost our natural immune system using small chemical non-university research institutes who defences against infections, but a micro- molecules, and in this way, they create are concerned about microorganisms: biome that does not function properly an equilibrium. Our own bodies benefit at the 2017 G20 summit in Hamburg, opens the doors to infections and other from this in a variety of ways. We want the heads of state and government lea- diseases. to learn how this works, in order to be ders of the most powerful countries in able to influence such microbial com- the world discussed the usual econo- The human-microbe relationship there- munities. mic and financial topics, but also tal- fore appears to be quite ambivalent: ked about diseases caused by microor- are there good bacteria and bad bacte- Which ones, for example? ganisms. Why is that? ria? The microflora in our intestines, for ex- Because infectious diseases are a major No, that would be too anthropomorphic ample. It is not only important for our and growing problem, here and around a perspective. There is no question that digestion, but it is also decisive for a the world. In Germany alone, 60,000 it is important to be concerned about in-

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Microscopic world with spruce (see also cover photograph): At the Institute for Microbiology, scientists study the interaction between tree roots and fungi.

fectious diseases and to do everything without microorganisms. We have a In order to understand why microbes possible to stop them from spreading. multitude of immunoreceptors, which coexist in one composition or another However, we must not forget that the exist exclusively to interact with various and what influence they have on their vast majority of microbes are comple- different microorganisms, because these environment and on their hosts, such as tely harmless to us or are even useful. can be either dangerous or useful to us. humans, plants and animals, we have There are an estimated three to five mil- This means that in the course of time, to conduct mechanistic analyses. For lion fungus species, of which only 150 microorganisms have formed and chan- this, we need a panoply of new me- are known to be pathogens. And what is ged us, just as we have also formed the thods: good computer model systems more, we live off microbial products: we microbial communities. Similar exam- in order to perform simulations; and eat bread, cheese and yoghurt—and we ples can also be found in plants, which new methods of optical and chemical drink alcohol (he laughs). have used the interaction with microor- analysis, with which we can observe ganisms to develop efficient defence the vital processes within the organis- So, does that mean we need microorga- strategies. There is a constant competi- ms in real time and in situ (in their real nisms more than they need us? tion between microbes and higher orga- surroundings). We want to image sing- That means that the coexistence, the nisms. le cells and molecules with the highest interaction between microorganisms resolution possible and be able to see and humans or other higher organisms What challenges must microbiological how individual microbes »talk« to one is the result of millions of years spent research therefore meet in the future? another and to us. And materials scien- evolving together. We are mutually de- What we have achieved to date is a tists are also required, because we need pendent on one another. What is cer- comprehensive analysis of microbi- artificial cells and organs, which we can tain is that microorganisms were the al communities. We can sequence and use to study and manipulate microbial first organisms on Earth—and they will compare their genomes and their me- communities. probably be the last. The evolution of tabolisms, their proteins and natural These are major research goals for all higher organisms always involved products. We can precisely describe the the years to come and in Jena we are interaction with microorganisms and organisms and the consortia they form. well-placed to pursue them. We expect this continues in the present day. We But describing is far from understan- this research to yield decisive findings can see this in our immune system, for ding. The next research step therefore for the treatment of diseases, for agricul- example, which would not even exist consists of function analyses. ture and for environmental protection. SCHWERPUNKTFEATURE 17

Hyphae of the yeast fungus Candida albicans (turquoise) and intestinal bacteria Proteus mirabilis (green) attack an intestinal mucous membrane cell (grey). The electron micrograph shows the process in the cell cul- ture, magnified 4,000 times (see p. 18).

© Sandor Nietzsche und Susanne Linde, Electron Microscopy Centre of the University of Jena

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»Dr Jekyll and Mr Hyde« in the intestine

Prof. Dr Ilse Jacobsen and her team examine how harmless inhabitants may become dangerous intruders. The team researches into the pathogenesis of systemic fungal infections. Together with other microorga­ nisms, facultative pathogenic intestine inhabitants, for example Candida albicans and Proteus mirabilis, assist us in suppressing other intestine pathogens and train our immune system. Nevertheless, they may also cau- se life-endangering infections, including sepsis. A decisive factor for the transformation of »Dr Jekyll« into »Mr Hyde« in the intestine microbiota is the interplay of microbes in the »ecosystem human«.

BY UTE SCHÖNFELDER

As humans, we are changing habitats da albicans can penetrate the cells of the —even in a complete isolation, we are intestinal epithelium and bore holes into never left alone. Humans and trillions of the barrier. microorganisms form a highly complex »Consequently, it is not only the fungus ecosystem. Carrying hundreds of vari- itself that may reach the surrounding ous species of bacteria, fungi and other tissue but also other microorganisms microbes around with us, we share as well. Both may infect internal organs nutrition and protect each other. This and, under circumstances, spread to means that it is not only our digestion the blood circulation resulting in infec- which benefits from our intestine micro- tions throughout the body,« explains biota. Increasingly, studies suggests that Ilse Jacobsen. In a worst-case scenario, the intestine microbiota also participate patients suffer from sepsis—a systemic in a variety of life processes, for instance inflammatory response affecting the from our immune response and circula- whole body. Approximately a quarter of tory system to our mental state. the infected persons do not survive such an infection (see p. 20). One of the most prominent »inhab- itants« of the human intestine is the What might lead to such a dramatic Prof. Dr Ilse Jacobsen is head of the research group Microbial Immunology at the Leibniz Institute for yeast Candida albicans. Despite the fact transformation? How is it possible that Natural Product Research and Infection Biology, that every human being has an indivi- Candida albicans abandons the peaceful Hans Knöll Institute (HKI) and Professor for Microbial dual composition of microbiota, Candida community of intestine population and Immunology at the University Jena. albicans can be found in the majority of turns against its host organism in such the population. Having a size of a few terrific manner? Paradoxically, one of micrometres only, these unicellular or- the risk factors is the progress of the ganisms usually live in balance with modern medicine. For systemic fungal other microorganisms as commensal infections affect already seriously ill pa- organisms not only in the intestine but tients in particular. »Patients in intensi- also in the oral cavity or on the skin. ve care often receive antibiotic therapy,« »Under certain circumstances, however, points out Jacobsen. However, this does this rather unspectacular fungus may not only mean a targeted reduction of become a truly life-endangering patho- germs, it may also lead to a particular gen,« says Prof. Ilse Jacobsen. As the illness. Professor of Microbial Immunology at The microbiologist further explains: the Leibniz Institute for Natural Product »Taking antibiotics may seriously influ- Research and Infection Biology, Hans ence the microbial life communities of Knöll Institute (HKI), she and her team the patient and disrupt their natural ba- do research into the reasons for such a lance.« Numerous studies prove that the serious change. Usually, the yeast cells changed constellation in the »ecosystem live isolated and have a round form. human« is particularly advantageous to However, the fungus is also able to Candida albicans and to a series of bacte- grow into long, multicellular filaments ria. They gain an advantage in terms of or hyphae. Using its »tentacles«, which growth and force other organisms to the may grow up to 100 micrometres, Candi- margins. Rubrik 19

Dr Maria Joanna Niemiec (left) and the master's student Isabel Auge are plating mouse excrement to culture medium in order to determine the microorganisms in there. They want to find out how yeast fungi and intestine bacteria communicate with each other.

Yeasts spur bacteria to produce more ing one: »In this case, almost every cell observed in the cell cultures are repro- toxin comes to its end,« sums up Dr Niemiec. ducible in vivo,« reveals Dr Niemiec. In »Here, we do see a synergetic, mutually this regard, studies on roundworms and Similarly as Candida albicans, various in- intensified effect of both pathogens.« mice are being planned. testine bacteria also belong to the facul- The first, yet not published findings tative pathogenic species and may cause from the Jena research team reveal the life-endangering infections, including reasons for the devastating effect. There A targeted-oriented prophylaxis sepsis. In the current research project are various indications that the bacteria against fungi CanBac by the Center for Sepsis Control Proteus mirabilis produce an increased and Care (CSSS), the researchers in the amount of toxin in the presence of Can- »Nonetheless, we can derive some use- Jacobsen’s team, their colleagues from dida albicans. This hemolysin is a protein ful aspects for the treatment of patients the HKI and the University examine which lyses, i.e. dissolve, the cell mem- in intensive care from the findings al- the interplay of the organisms among brane of the host organism. As a result, ready,« makes Prof. Jacobsen clear. Ac- themselves and towards their host—the the cells die. »Essentially, the fungus cording to her, every seriously ill pa- human. makes the bacterium more toxic,« illus- tient should undergo an individual risk »We cultivate intestinal absorptive cells, trates Prof. Jacobsen. In comparison to assessment on how probable an emer- so-called enterocytes, and infect these this, the »aggressiveness« of the fun- gence of sepsis may be. »If, for example, with combinations of the examined gus—this being pathogenic, too—is not Candida albicans reduces other microor- microorganisms,« explains Dr Joanna stimulated by the bacterium. Indeed, ganisms after the patient has received Niemiec their experimental approach. Candida albicans may produce a lethal an antibiotic therapy and the germ con- »In the project, we want to understand toxin, i.e. candidalysin. However, it is tent of Proteus mirabilis or another com- how fungus and bacteria influence each rather unlikely that its production may parable pathogen increases at the same other regarding their pathogenicity.« be additionally boosted by a co-infec- time, a concrete, serious risk for the pa- Dr Niemiec is a postdoctoral researcher tion with Proteus mirabilis. tient exist.« and leads the project team CanBac with- In her opinion, a prophylactic therapy in the Jacobsen’s research group. In the current examinations, the re- concentrated on fungi is advisable in Among others, the researchers study searchers want to find out by which che- such cases. On the other hand, Prof. Ja- the interplay between Candida albicans mical »means of communications« the cobsen is critical of general prophylac- and the intestine bacterium Proteus mi- microbes communicate with each other. tic measures against fungal infections rabilis. The cell culture shows that both It is already clear that also other yeast using agents. »All in all, there are only microorganisms, respectively, may da- fungi, for instance the common baker’s a few antifungals; if they are generously mage the intestinal cells on a limited. If yeast Saccharomyces cerevisiae, spur Pro- used for prophylaxis, the fungi may be- the intestine cells, however, are infected teus mirabilis into the intensified produc- come resistant, similarly to antibiotics.« by both pathogens at the same time, the tion of hemolysin. »Additionally, we Therefore, these agents should be used picture the researchers see is a strik- also want to find out whether the effects for specific purposes only.

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Achilles’ heel immune system

in the world. In Germany, for instance, Despite modern medicine—or perhaps because of it—sepsis ranks approximately 280,000 new cases of among the most frequent causes of death in Germany. Although sepsis occur every year killing almost a sepsis is predominantly triggered by bacteria, it is fungi, for example quarter of the affected patients. The si- tuation in Jena reflects these data. »Out Candida albicans, which increasingly cause a deadly course. Prof. Dr of 400 patients, we lose around 100 be- Michael Bauer investigates severe and life-threatening infections at cause of the insidious disease,« reports the Jena University Hospital and at the Center for Sepsis Control and Bauer, who is also the speaker of the Care (CSCC). In order to understand how microorganisms communi- CSCC. Sepsis may occur as a complica- cate within the human body, he wants to learn from biologists. tion of any infection, for example pneu- monia, tonsillitis or urinary tract infec-

BY JULIANE DÖLITZSCH tions, not to mention those following injuries or surgical procedures. Thus every medical speciality has to deal with the problem.

It is not only its name which seems of control and the stress response of the In most cases sepsis is caused by bacte- devastating, it is devastating itself: sep- body harms its own tissue and organs: rial pathogens, for instance Staphylococ- sis is a false, self-destructive reaction »Instead of directing its full rage against cus aureus or Escherichia coli. When the of the human body. »According to the the pathogen, the immune system turns disease seems to be overcome, danger current definition, sepsis is an organ against the host itself. The body’s repair can be still imminent: »A second sep- failure resulting from inadequate re- systems fail.« tic episode is, in more than 30 percent sponse of the organism to an infection,« Sepsis may lead to shock, multiple of the cases, due to a fungal infection,« explains Prof. Dr Michael Bauer, an ex- organ failure, and ultimately to death, specifies Michael Bauer. »It is rather dif- pert in intensive care medicine at the especially if it is not recognized ear- ficult to detect fungi and our diagnostic Jena University Hospital. During sep- ly and treated promptly. Sepsis is the methods are not fast enough. Detection sis, a life-threatening infection gets out leading cause of death from infection using blood cultures takes days, but pa- SCHWERPUNKTFEATURE 21

INFECTIONS, SEPSIS AND THEIR CONSEQUENCES

Infectious diseases are on the rise throughout the world. More and more pathogens are becoming resistant to antibiotics and thus threaten the health of many people. A »postanti- biotic era« is looming, in which harmless diseases may end up tragically. A network of lead- ing scientific institutions led by the Leibniz Association and with participation of the Fried- rich Schiller University Jena is calling on the next German federal government to increase its support of the struggle against multiresistant pathogens. Research on new therapies and diagnostic procedures requires an improved interdisciplinary collaboration in hospitals as public-private partnerships. In a joint call for action, presented in November 2017 during the World Antibiotic Awareness Week in Berlin, the signatories claim that the patients should benefit from research results earlier than it has been the case until now. For more details on the appeal, please refer to: www.leibniz-ipht.de/fileadmin/user_upload/Aufruf_Infektionskrankheiten.pdf

Not only sepsis (colloquially: »blood poisoning«), but also the consequences of this disease pose a heavy burden on patients and their relatives. After awakening from an artificial coma, which might have lasted a few days or several weeks, many patients are unable to move. Often they have to relearn particular body movements whereas the body and the damaged organs have to gradually regain their normal functions. Quite often a lack of oxygen during sepsis cau- ses serious tissue damage on peripheral limbs. As a result, the dead tissue has to be surgically

On the left photo: Prof. Dr Michael Bauer is one removed, which can include amputations. In addition, patients may face long-term conse- of the three speakers of the Center for Sepsis quences, for example weight loss, fatigue, headache, joint and muscle pain. Further problems Control and Care (CSCC). At the Jena University include cognitive impairment, such as poor concentration and loss of memory, deafness, and Hospital, the expert in intensive care medicine paralysis. Finally, the experiences in intensive care can seriously affect patients’ mental health and his colleagues treat around 400 patients per and require therapeutic intervention (see the interview on p. 22). year suffering from sepsis. For about a quarter of them, the disease is fatal. Among frequent cau- ses of sepsis are bacterial and fungal infections.

tients pass away within a few hours.« to him, the human body usually har- systems and how they communicate,« It is therefore critical to close funda- bours such germs without developing Prof. Bauer is firmly convinced. »In this mental research gaps. The Jena research disease—they only trigger disease un- regard, I want to learn from biologists.« campus InfectoGnostics, for instance, der certain circumstances. The fungus Applying their findings to medical prob- has already been working on better and Candida albicans, for example, colonizes lems might lead to completely new per- faster procedures. Three partners join more than 50 percent of the population: spectives beyond the simple concept of their forces and share their expertise in it can be found in the mouth and in the aggressively treating all pathogens with the research campus: the Leibniz Insti- throat, in the genital region or in the di- antibiotics. Otherwise the number of tute for Natural Product Research and gestive system (see p. 18). multiresistant germs will continue to in- Infection Biology, Hans Knöll Institute crease which—in the worst case—may (HKI), the Jena University Hospital, and »The human immune system limits the end in a »postantibiotic era« (see the box the Friedrich Schiller University Jena. success of the modern medicine—it is above). Bauer points out the urgency of this re- the Achilles’ heel,« Bauer illustrates. To search topic: »The number of the septic be more accurate, many drugs and ther- infections is increasing.« Taking the mo- apeutic procedures affect the immune Body has to find the suitable stress dern, highly advanced medical techno- system, and make it more susceptible response on its own logies into consideration, this may be to pathogens—also to those germs re- surprising at first. However, this very siding in the body, for instance Candi- »Finally, a better understanding of medical care provides the favourab- da albicans. In particular the intestinal microorganisms will help us to find no- le conditions for invasive infections. microbiome, also known as gut flora, vel approaches to strengthen the body’s »More and more people achieve rather which consists of millions of microorga- defence and the immune system. The advanced ages. Often, persons over 80 nisms, is »a decisive factor for the hu- body itself should find a better stress years receive a new knee joint or a hip man health«. When these microbes turn response to sepsis and become more joint,« explains Bauer. »But even a suc- against the body, physicians are often at resistant,« hopes Michael Bauer. »To cessful surgery may weaken the immu- their wits’ end. achieve these goals, it is our top priority ne system. At that very moment, facul- »It is thus essential for us to understand to team up and to combine our inter- tative pathogens often hit.« According how microorganisms function in eco- disciplinary expertise.«

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»We take the therapy to the patient«

Sepsis is the most frequent cause of death among infectious diseases. Those having survived it not only suffer from considerable physical impairments, also their mental health is impaired because of the experience of a life-threatening disease and intensive care. The experiences change the patient’s life and that of the partner. A therapy is often inevitable to overcome the experiences. One of the projects at the Center for Sepsis Control and Care (CSCC) aims to help the persons affected by offering them an Inter- net-based writing therapy. The treatment »zwei leben« is accompanied by a study examining its efficacy. More about the project and the therapy in the following interview with the psychologists PD Dr Jenny Rosendahl (project manager) and Romina Gawlytta (project coordinator).

INTERVIEW: JULIANE DÖLITZSCH

In Jena, the research on sepsis is rather ment actively, too, and are being treat- How does your project help them? intensive at the moment. Your project ed themselves if they also suffer from Rosendahl: After being affected by sep- was launched in February 2016. Could PTSD. If the partners are not affected, sis, the patients are discharged even you explain your approach please? they still receive information on the the- if they still have residual symptoms. Rosendahl: As part of our research at the rapy and attend the first telephone in- The process of physical recovery often CSCC, we have been dealing with the terview. This is reflected in the project’s evokes negative memories. As a conse- psychological long-term consequences name zwei leben; firstly, it is about both quence, a trauma therapy is necessary. of those who had survived sepsis. Some partners, secondly, the patients often However, long waiting times and great of these consequences are, for instance consider their life after intensive care as distances, particularly in the countrysi- anxiety, depression, adjustment disor- their second chance. de, often hinder the patients. We there- der, and post-traumatic stress disorder fore offer an Internet-based writing the- (PTSD). This may occur as a psychologi- So the partners could also be affected, rapy and take the therapy to the patient. cal response to an extremely overwhelm- couldn’t they? In recent years, psychological treatment ing event, i.e. a trauma. For example, a Gawlytta: Yes, some of the partners are via the Internet has become an import- trauma may be a traffic accident or expe- also affected due to their experiences. ant treatment method. Various research riencing violence, but also a death threat While the patients are in a life-threa- projects have been working on its im- in extreme medical cases. For many, the tening condition over a period of se- provements. In comparison to the com- helplessness encountered then is ines- veral days or even weeks the partners mon face-to-face psychotherapy, the capable. are also in a stressful situation. They therapist and the patient are in contact do not know whether their partner will with each other via computer. What are the effects of PTSD? still be alive when they will be back for Gawlytta: Patients often have nightma- a visit in the hospital. Sometimes they What are the advantages of the Inter- res, they experience flashbacks and in- fear the situation when they have to net-based writing therapy? trusions reminding them of intensive decide whether the life-sustaining me- Rosendahl: In particular it is the fact that care. They also suffer from sleep distur- dical devices should be switched off or it can take place everywhere and at any bances or may have a lack of concentra- not. Many of the partners still deal with time. Patients do not have to wait for tion. As a result, the quality of life may these memories even weeks or months a therapy as it is common to the face- be reduced and they may encounter an after their partner has already left the to-face therapy and can plan their wri- enormous emotional stress frequently. intensive care unit. ting sessions at home easily instead. Most of them are not able to overcome Especially for disabled persons it is a the experiences without professional as- How many patients suffer from PTSD? real benefit. In addition, some patients sistance. Rosendahl: The numbers vary depending may become more accessible since they on the respective study. Generally, every do not have to sit in front of their the- What is new about the project? fifth patient with sepsis and every fifth rapist. For some of them, it may be ea- Rosendahl: In our study, we examine the partner suffers from PTSD. If the pati- sier to write about feelings of guilt and efficacy of the Internet-based writing ents themselves are affected by PTSD, shame. therapy which is applied after intensive often their partners are affected, too. care of a critical illness. In this regard, They share the same fate, yet from two The project »zwei leben« is a cooperati- we apply a new approach: the partners perspectives. on project—with whom do you work? of our patients participate in the treat- Rosendahl: On site, we cooperate with an SCHWERPUNKTFEATURE 23

PD Dr Jenny Rosendahl (right) and Romina Gawlytta, psychologists from the Institute of Psychosocial Medicine and Psychotherapy at the Jena University Hospital.

IT specialist who administers the portal. partner in which they should find cannot take part in our study. Other- In Berlin, we collaborate with Prof. Dr some comforting and sympathetic wise we cannot measure the success of Christine Knaevelsrud, and two other words regarding the past and current our offer. Apart from those, neither per- therapists from the Freie Universität. strain. Moreover, they should point sons addicted to medication or alcohol They are responsible for the therapeutic out their belief in the partner’s abilities nor those with suicidal tendencies can part—they read the texts and give their and competencies. The letter is com- participate. Of course, we do support feedback to the participants. Hav- pletely confidential and the therapists those persons in finding an appropriate ing applied the Internet-based writing do not read it. If both partners partici- therapy for them. However, sepsis is not therapy for treatment of traumatic ex- pate in the therapy, they have to write an exclusive criterion. As a result, also periences of refugees and of soldiers letters to each other. someone who underwent intensive care or persons traumatized in World War because of other reasons may participa- II, they contribute their expertise to the Have you received any feedback from te in the study. project. the participants, yet? Gawlytta: Yes, we have. After the treat- What will happen next? What do the participants write about? ment had been completed, I called the Rosendahl: We will have been recruiting Gawlytta: The first three texts have a bio- participants for a diagnostic interview. participants until the summer 2018. Our graphical focus. The participants write Although some of them were sceptical aim is to include 70 couples in total. Up about their childhood, their youth, and before starting the treatment, their feed­ to now, 14 couples have already begun their life before the disease. In the fol- back is positive without exceptions. their treatment or completed it. We lowing four texts, they are supposed to They are glad that they had taken part would thus welcome any further pati- reflect on their experiences at the inten- in the project. They do not have as many ents. At the beginning of 2019, the study sive care unit and to describe their me- nightmares and flashbacks as before. will have been completed. When we are mories and their fears concerning the in- And even if some occur, they can cope able to prove the efficacy, we would like tensive care as detailed as possible. The with them in a different way. to continue the project. We are comple- last three texts shall give the patient the tely sure that the persons affected do be- chance to think about the experiences You carry out diagnostic telephone in- nefit from the therapy. from another point of view. They should terviews to find out suitable candida- not consider themselves as victims any- tes. Who cannot participate in the pro- How might the project »zwei leben« more since they have already overcome ject »zwei leben«? evolve in the long term? the disease, they are not helplessly ex- Rosendahl: Unfortunately, all who do not Rosendahl: For example, we might of- posed to the situation anymore, and can have a partner—our study focuses on fer our treatment to individuals so that deal with their future expectations. couples. singles or people whose partner died of sepsis could attend it, too. I can also Rosendahl: Apart from these texts, the Gawlytta: Everyone who is undergoing a imagine internationalizing the project. partners write a letter to the affected psychotherapeutic treatment elsewhere

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Rapid test shows antibiotic resistance

Ironically, it is the very use of antibiotics in the fight against infectious diseases that is partly responsible for one of the most pressing health problems of the 21st century. Increasingly, pathogens are adapting to the active substances in antibiotics, thereby making some drugs ineffective. Hardly any new antibiotics have been developed over the last 20 years. In Germany, around 500,000 patients a year contract a hospital- acquired infection—and 15,000 of them die as a result. Faster and more precise diagnostic methods could lead to more targeted use of antibiotics, thus reducing unnecessary prescriptions. Researchers from the University of Jena, the Leibniz Institute of Photonic Technology (Leibniz-IPHT) and the Center for Sepsis Control and Care (CSCC) offer a solution to this problem.

BY SEBASTIAN HOLLSTEIN

»All organisms—and especially micro­ he would be able to prescribe a targeted stics Research Campus. At the centre organisms—adapt to their environ- remedy that only affects the bacterium of this procedure is a chip of about four ment in order to ensure the survival concerned. However, this usually re- square centimetres. On this chip pati- of their species,« asserts Prof. Jürgen quires elaborate diagnostic procedures, ent samples, such as urine, are brought Popp. »Resistance to antibiotics can which can take up to 72 hours and hin- into contact with antibiotics, which re- therefore not be prevented—but it can der rapid treatment of the illness. »So act with the bacteria in the sample. To be delayed.« To achieve this, a doctor we need tests that quickly show how be able to examine them more closely, would have to be in a position to pre- a pathogen reacts to an antibiotic,« ex- dielectrophoresis is used to concentrate scribe the drug that specifically treats plains Popp. the pathogens on the chip into an area the infection in question. However, up of just a few micrometres. To this end, to now it has been usual to tackle a pa- Popp, who heads the Institute of Phy- the surface of the chip carries electrodes, thogen using broad-spectrum antibio- sical Chemistry at the University of which generate inhomogeneous electric tics, which also kill other bacteria. This Jena and leads the Leibniz-IPHT, has fields when a voltage is applied. In turn, encourages many more bacterial strains developed such a procedure over the the effect of these fields holds the bac- to develop resistance. If a doctor knew last few years, together with colleagues teria in place at specific points, without exactly which pathogen was involved, from the CSCC and the InfectoGno- damaging them. If the pathogens are SCHWERPUNKTFEATURE 25

Photo left: Raman spectroscopy using the chip that not only allows pathogens to be clearly shown within a few hours. This innova- tion from Jena can also indicate whether the pathogens react to the antibiotics adminis- tered or whether they show resistance. This saves valuable time in treating patients. Photo right: Prof. Jürgen Popp and Prof. Ute Neugebauer head a team of scientists that developed the new system of analysis.

concentrated in this way, researchers reason, Popp, Neugebauer and their a first prototype within two to three can carry out the actual analysis. »For colleagues have developed a rapid test years; initial contacts have already been this, we use Raman spectroscopy—an that specifically verifies whether or not made with partners from industry.« analytical method based on optical light this pathogen reacts to vancomycin. In In general, Popp is very committed to scattering. It enables precise identifica- this case too, the researchers use Ra- interdisciplinary cooperation, and he tion of individual bacterial strains,« says man spectroscopy to get their results. has found optimal conditions for this Prof. Ute Neugebauer, who is closely in- They bring samples of the bacteria into in Jena. The InfectoGnostics Research volved in developing the new analysis contact with the antibiotic and observe Campus alone enables fruitful coopera- system. »Bacteria are irradiated with changes in the spectral pattern. After tion with doctors, scientists from other light and the light scattering is ana- just 90 minutes or so, it is possible to disciplines and partners from industry. lysed. Each bacterial strain then shows see whether or not the pathogens re- In addition, the proximity to Jena Uni- an individual, unique spectral pattern, act to the drug and die. Even with the versity Hospital is crucial, because such with which the pathogen can be clearly necessary preparation and post-process- a method of analysis cannot be created identified.« For this, the scientists use ing, the procedure takes at most three- without knowledge of the daily routines multivariate statistical algorithms in or- and-a-half hours. This method of analy- at a hospital, medical work processes der to match the measured patterns to sis can also be applied to other patho- and safety standards. It is therefore im- known spectral patterns of bacteria in a gens and antibiotics. Furthermore, it portant that his colleague, Ute Neuge- database. should be possible to test several anti- bauer, for example, does research in the biotics simultaneously on the recently CSCC at Jena University Hospital. To treat patients successfully, it is neces- developed chip. sary to check not only the pathogen, but Popp also stresses, however, that also for existing types of resistance. In technical developments alone are not developing the chip system, the rese- Easy-to-use chip system for doctors to sufficient to combat antibiotic resistan- archers in Jena focused first on entero- start a correct antibiotic treatment ce, because what use are even the best coccus bacteria. Some strains of these methods if they are not applied for rea- intestinal bacteria can cause urinary »Our aim now is to develop a closed ra- sons of cost? »It is therefore important tract infections, but also sepsis and en- pid test system that doctors can use both to bring the health insurance funds on docarditis. As early as 30 years ago, in the hospital and in a doctor’s surge- board to address those aspects in the it was reported that some enterococci ry,« explains Jürgen Popp. »For the sys- next few years.« The urgency expressed had become resistant to the antibiotic tem you need of course the chip as well by the current figures on hospital-acqui- vancomycin, and this has become a as associated reading devices, which red infections should raise awareness of worldwide medical problem. For this provide the result. We want to present the problem.

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Drops of blood in focus

At the Leibniz ScienceCampus InfectoOptics, scientists in the research project BLOODi are developing a dynamic haemogram. They want to use new optical technologies to recognise infectious diseases and their pathogens in whole blood in the fastest way possible. In order to discover how individual blood cells behave in the case of an infection and how they interact with pathogens, biologists, physicists, bioinformaticians and mathematicians need to pool their expertise and find a common language.

BY JULIANE DÖLITZSCH

BLOODi is as gruesome a project le, BLOODi reflects the wider scientific ensure that BLOODi is well-positioned, name as you could imagine and it con- landscape here is quickly apparent to not only as regards its interdisciplinary jures up horrifying images in my mind. me when I look at the organisational nature, but also its multinationalism. However, BLOODi is anything but structure and then meet a number of re- Three of the doctoral candidates come bloodthirsty. On the contrary: the aim searchers from the project group. They from Germany and the others hail from of the project, which brings together include biologists, physicists, mathe- Italy, India, Russia and Syria. The young the University of Jena and a number maticians and bioinformaticians. One researchers’ fresh ideas and open- of non-university research institutes, is goal unites them all: »With the help of minded outlook on research contribute that a single drop of blood should ideal- optical technologies, we want to develop towards the enthusiasm for innovation ly be enough to provide extensive infor- a dynamic haemogram and use it to en- that characterises BLOODi. mation. The lower-case »i« in the name able the rapid and targeted treatment of stands for Imaging and the complete infectious diseases,« explains Prof. Marc project name is »Whole Blood Imaging«. Thilo Figge, who heads the project. »The Short distances between labs The objective is to capture the dynamics special feature is that we want to leave of the blood components by means of the blood intact, in order to observe the The project, which was launched 18 microscopic »snapshots«, in order to be interactions between cells. To achieve months ago, is based very strongly on able to say as quickly as possible which this, we are bringing together various exchanges between researchers, says pathogen has triggered an infection. different scientific disciplines and in- Figge. »We regularly get together in a stitutes.« This does not seem at all easy large group to discuss results and new In Jena, short distances and short lines to me, and Prof. Figge concurs. »We approaches. And of course, we also of communication are important—that first had to get talking to each other and make contact in smaller groups, when- much has become clear to me. Easy ac- develop a common basis and langua- ever the need arises.« Communication cessibility is a feature of the town, but ge,« the physicist recalls. The BLOODi is greatly eased by the fact that every- also of the University and other research team comprises 18 researchers, inclu- one is close together on the Beutenberg institutes. The fact that, on a small sca- ding seven doctoral candidates who Campus. In just a few minutes you can FEATURE Rubrik 27

Doctoral candidate Alessandra Marolda is studying neutrophil granulocytes, by comparing two blood samples from the same person. One sample is infected with the yeast Candida albicans and the other is not. Investigations using a laser scanning microscope reveal significant differences between the neutrophils from infected blood and those in the control sample.

be knocking on the door of a fellow re- »At the beginning we do indeed inves- the isolated neutrophils from the infect- searcher, so that you can discuss work tigate single cells, but without marking ed blood can indeed be distinguished and swap ideas. them.« The cells are thus not stained, from those of the non-infected blood: but are left as intact as possible, in order their shape has altered slightly, as they While Alessandra Marolda, Italian doc- to produce valid results in spite of the are somewhat flatter. »Their morphoki- toral candidate at the Leibniz Institute cells having been extracted. netics have been influenced by the pa- for Natural Product Research and In- thogen,« explains Alessandra Marolda. fection Biology—Hans Knöll Institute In the next step, she is going to study, (HKI), explains her role in BLOODi, I Neutrophils react to fungus infection by infecting the blood samples, how the am aware of other researchers in the lab. immune cells react to other fungi and In the background, I can hear the eager To this end, she took two blood samples bacteria: in exactly the same way? Dif- whispering of the other project mem- from the same person, infecting one ferently? Do they only help to signal an bers, who are not chatting about what sample with the yeast and leaving the infection or can one use their characte- they did at the weekend, but are discus- other as a control. »After one hour, I iso- ristics to identify a specific pathogen? sing current results from the lab. lated neutrophil granulocytes from both How do other blood cells behave? In the Ideally, at the end of the project it would samples,« says Marolda. These cells, of- case of sepsis, for example, starting treat- be possible to investigate whole blood, ten known simply as neutrophils, are by ment as early as possible is crucial to its with as little effect as possible on the far the most common white blood cells. success—a rapid identification of the blood samples, the young biologist Ma- »As part of the innate immune response, bacteria and the appropriate medical re- rolda explains. Scientists have thus far they help to identify and destroy micro- sponse can, in extreme cases, mean the been unable to do this. Nevertheless, organisms—for that reason, it seem- difference between life and death. she has already reached a small milesto- ed to us promising to examine them ne with her investigations in the initial more closely,« adds Marolda. When Impressed by the significance of the in- stage of the project at the Centre for In- I make initial attempts with the laser vestigations, I leave the laboratory. The novation Competence (ZIK) Septomics. scanning microscope, I too can see that others also stop their shop talk, which

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Prof. Dr Thilo Figge (left) and doctoral candidate Ivan Belyaev analysing experimental data. Here they take a closer look at images of granulocytes produced by time-lapse microscopy.

now touches on the similarities between such as proteins, lipids and DNA. If we what they want to study and what they the microscopes used by biologists and irradiate the whole blood with two la- want to find, but they are not able to physicists. It appears that they cannot be ser pulses, we selectively cause different create the necessary methods.« The easily compared in the case in question. molecules to oscillate and observe their close cooperation between laser physi- Together, we swap lab coats for jackets distribution in the cells. As the oscilla- cists, biologists and immunologists thus and set off, arriving just a few minutes tion spectrum of the cell is as specific as stimulates fruitful research ideas and later in a physics lab of the Abbe Center a fingerprint, we can use it to identify the possibility of making them a reality of Photonics. the biochemical composition. This is through the collaboration between the how we find the neutrophils in whole various disciplines. blood, for example.« Microfluidics gives information on This is important, because in the physics composition of blood samples lab, too, researchers aim to have as little Time-lapse microscopy makes diffe- impact as possible on the blood samples rences visible Now equipped with shoe covers, I ex- and, unlike in the flow cytometry proce- amine a microscope. Under the lens is a dure commonly used to date, they do And because someone is also needed to chip stamped with fine, winding lines. not want to mark cells. Using oscillation analyse and interpret results from the Susanne Pfeifenbring, who works here spectroscopy, also called Raman spec- laboratory, scientists such as Prof. Fig- most of the time, explains to me what troscopy, they could determine in this ge himself and doctoral candidate Ivan this is all about. This chip measuring way which cells are involved and, ideal- Belyaev complete the team. At the Cen- about one by one-and-a-half centimet- ly, whether they have been in contact ter for Systems Biology of Infection at res forms the foundation of drop-based with particular pathogens. »Combi- the HKI, which we visit last, the experi- microfluidics. Physicist Pfeifenbring, ning non-linear laser spectroscopy with ments are mathematically analysed. For who is doing her doctorate at the Leib- microfluidics in order to examine whole example, they receive data from Ales- niz Institute of Photonic Technology blood is completely uncharted territo- sandra Marolda and take a closer look (IPHT) within the framework of BLOO- ry,« adds Susanne Pfeifenbring. at the development of neutrophils in the Di, responds to my puzzled look by individual »snapshots«. The sequences explaining further: »We place a drop of As we slowly make our way back out­ of images produced using the time- blood on the chip and examine the blood side, Marc Thilo Figge once again high- lapse microscope—also called Live Cell cells using non-linear oscillation spec- lights the key feature of BLOODi: »Here, Imaging—enable researchers to deter- troscopy.« Little the wiser, I study the physicists develop new optical methods mine dynamic characteristics of the cell chip, but Pfeifenbring continues: »Every for which they on their own do not see shapes. »This allows us to capture diag- cell consists of various macromolecules, any necessity. And our biologists know nostic criteria for cells under health and SCHWERPUNKT 29

»BLOODi« is a subproject of the Leibniz ScienceCampus »InfectoOptics«. Resear- chers from both Life Sciences and Optics/ Photonics are working closely together in an effort to understand and fight infectious diseases better with the aid of innovati- ve optical technologies. Project partners include Friedrich Schiller University Jena, the Leibniz Institute for Natural Product Re- search and Infection Biology—Hans Knöll Institute (HKI), the Leibniz Institute for Pho- tonic Technologies (IPHT), the Fraunhofer Institute for Applied Optics and Precision Engineering (IOF), the Institute of Molecular Pathogenesis at the Friedrich Loeffler Ins- titute, the Federal Research Institute for Animal Health (FLI), as well as BLINK AG.

Fundamental to droplet-based microflui- dics is a chip (Photo).

disease conditions,« explains Belyaev, who is doing his doctoral research at the HKI. He refers to some diagrams on his computer, which are based on investigating the morphokinetics of the neutrophils. »As a result, we know that we should take this aspect into account when performing the microfluidics tests with whole blood. That takes us a big step further.« The Russian physicist is working on the BLOODi project for one reason: »Scientific curiosity.«

It is clear to me that this is also what drives his colleagues. With BLOODi, Alessandra Marolda values the fact that blood is studied in different ways and the results are brought together in the group. »Here, we approach a problem from various different angles and try to solve it together,« she notes. She and the other researchers have a good two years left for this work, after which the pro- ject will come to an end. In view of the significant initial results, Figge is opti- mistic. »We can learn a lot from the dy- namics of whole blood. The snapshots that we have obtained so far give us hope that we will find characteristic biomarkers for pathogens, and that in Doctoral candidate Susanne Pfeifenbring checks the setting of a laser using an infrared viewing device. future we will be able to make quicker In the BLOODi project, blood cells are irradiated with laser pulses in order to find out, by means of their oscillation prognoses regarding infections.« spectrum, which blood cells are involved and whether they have had contact with pathogens.

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Termites have »green fingers«

In a termite colony, there is—quite literally—the right chemistry. Busy termites cultivate a fungus in large fungus gardens and feed on them. They are assisted by bacteria in protecting this valuable source of nutrients. These live in the termites’ gut and in their garden, and produce natural products that prevent hostile fungi from infesting the termite mound. Christine Beemelmanns, with her team at the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (HKI), is investigating the relationship between host and bacteria, and in the process she is discovering new natural products.

BY MONIKA WEISS

We humans are colonized by many dif- Termitomyces in order to feed on it,« ferent microorganisms. Not only have explains Beemelmanns. Many different we become used to one another, we factors have to be in equilibrium for are also interdependent, as evidenced such a highly complex and fragile so- by our intestinal flora, for example ciety as that of the termites to remain (see p. 18). Although a few bacteria intact. or fungi frequently cause serious ill- In addition to abiotic factors such as the nesses, we could not survive without composition of the soil, it is the interac- most microorganisms. The same is tion between the organismic partners true of other organisms that coexist that is of decisive importance. Only if with microbes. For example, microor- the fungus used as a source of nutriti- ganisms in the root environment in on and the termites’ supporting micro- the soil have a symbiotic relationship bes are in a balanced relationship can with plants and help them to absorb such a complex system survive. Bioac- nutrients. And insects, too, have their tive substances, as they are known, are own very individual intestinal flora, on particularly important in this process, which they depend. because they serve the organisms con- cerned as signal and communication substances. Termites create gardens in their In this way, the microorganisms regula- mounds to cultivate fungi te their interactions and keep the system in equilibrium. In a similar way to hu- Mound of a Macrotermes colony »In the gut and the fungus gardens in South Africa. man beings with their complex micro- of termite species that cultivate fungi, biomes, insect communities form a kind we find what are called actinobacteria. of superorganism. However, these eco- They play an essential role for the in- logical systems are also vulnerable and sect community,« says Beemelmanns. are occasionally infested by pests or suc- The chemist leads a junior research cumb to infections. For example, parasi- group at the HKI, which is studying tic fungi can overrun the vital nutritio- the interrelationships between micro- nal fungus and cause the entire colony bes and their host at the chemical level. to collapse.

In 2015 and 2016, together with an in- Christine Beemelmanns’s junior re- terdisciplinary research group, Bee- search group is working on these micro- melmanns undertook expeditions to be-host relationships. She believes that South Africa, where fungus-cultiva- they hold great potential for finding ting termites live. With her colleagues, new natural products that could be she took samples from termite mounds: used in fighting human infections, for »We had to dig deep in order to reach example. Instead of randomly extrac- the termites’ fungus garden,« she adds. ting substances from samples, Beemel- »Similar to our cultivation of grain, ter- manns’s team first studies bioactive mites cultivate a fungus of the genus natural products within the organismic SCHWERPUNKT 31

Termite queen and king of the species Macrotermes natalensis. The queen (left) can grow to a length of 15 centimetres. Clearly visible is her enlarged abdomen for egg produc- tion. The king (right) reaches a size of only two to three centimetres. The queen is surrounded by a number of »workers« and small »soldiers«. The workers cultivate the fungus gardens and supply the queen and king with food. The soldier termites protect the gardens and the royal couple.

relationships to determine their possib- called, along with a few other natural ments, the researchers discovered that le biological function. This enables the products that have been found, prevent these active substances are also effec- researchers to kill two birds with one the harmful fungus from infesting the tive against the bacterium Pseudomonas stone: at the same time as finding new termite mound. That is to say, they form aeruginosa. This is an interesting finding, natural products, they gain a better a natural pesticide combination, which in particular because Pseudomonas ae- understanding of fundamental mecha- supports the termites in cultivating their ruginosa—a typical hospital-acquired nisms in complex symbiotic systems. food source. bacterium—can trigger serious wound »We have already found a few new mo- infections in patients. Such »gram-nega- lecules,« says Beemelmanns. One of the tive« bacteria are difficult to tackle. The molecules formed by the actinobacteria Active substances turn fungi into researchers in Jena therefore thought in the termites’ gut is of particular in- parasites and disarm hospital-acquired that they had a potential new substance terest to the researchers, because it has bacteria for treating wound infections. However, an as-yet-unknown structure. It is a hy- the substance turned out to be toxic, brid molecule that is composed of three In further investigations, Christine Bee- so that it was unsuitable for use as an different building blocks—a sugar, a melmanns and her research group ex- antibiotic for humans. »We have other polyketide and an amino acid—through amined another parasitic fungus more substances in the pipeline, however, the interaction between many different closely. They observed that this fungus, which we hope will show better phar- enzymes. »The final finished molecu- of the genus Pseudoxylaria, acts like an macological characteristics,« adds Bee- le is biologically inactive, as far as we invasive weed, overrunning the fungus melmanns with confidence. have been able to assess that to date. that is essential to the termites. Beemel- However, some intermediate products manns explains how this works: »From The HKI, together with the University show antimicrobial activities,« explains this harmful fungus we were able to of Jena, is currently applying for a pa- Beemelmanns. The natural product isolate cyclic tetrapeptides, which are tent for a new natural product, which researcher and her team assume that probably in part responsible for its could be used in developing a new drug these tropolone derivates, as they are parasitic lifestyle.« In further experi- for cancer therapy.

Original Publication Contact Beutenbergstraße 11a Isolation, biosynthesis and chemical modifi- Dr Christine Beemelmanns 07745 Jena, Germany cations of rubterolones A–F, rare tropolone Leibniz Institute for Natural Product Research Phone: +49 36 41 53 21 525 alkaloids from Actinomadura sp. 5—2 (2017), and Infection Biology – Hans Knöll Institute Email: [email protected] DOI: 10.1002/chem.201701005 (HKI) www.leibniz-hki.de

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»Fungus gardens« established by termites, with white fruiting bodies of the garden fungus Termitomyces. The oval fruiting bodies grow to a size of 1 cm.

Infected fungus garden with harmful fungus Pseudoxylaria. The parasite acts like a »weed«, overrunning the nutritional fungus essential to the termites. SCHWERPUNKT 33

Agar plate with green algae cocultivated with bacteria (center) and bacterial extracts re- spectively. In the center algal growth arrest is visible as a halo.

Ambush in a petri dish

Prof. Maria Mittag and Dr Severin Sasso If green algae of the species Chlamydomonas reinhardtii meet of the Matthias Schleiden Institute (Uni- Pseudomonas protegens bacteria, their fate is sealed. The bacteria, versity Jena) and Prof. Christian Hert- weck of the Leibniz Institute for Natural measuring only some two micrometres, surround the algae, which Product Research and Infection Biolo- are around five times larger, and attack them with a deadly toxic gy – Hans Knöll Institute (HKI)—report cocktail. The algae lose their flagella, which renders them immobile. in the journal Nature Communications. The green single-celled organisms then become deformed and are no longer able to proliferate. The chemical mechanism underlying this Orfamide A, as the substance is called, extremely effective attack has now been uncovered by botanists and is a cyclic lipopeptide which the bacte- natural product chemists. ria release, together with other chemical compounds. »Our results indicate that

BY UTE SCHÖNFELDER orfamide A affects channels in the cell membrane, which leads to these chan- nels opening,« explains Dr Severin Sas- so. »This leads to an influx of calcium ions from the environment into the cell It is a gruesome spectacle that meets the even smaller bacteria gather together interior of the algae,« adds the head of eyes of Prasad Aiyar as he looks down into swarms, which surround the algae. the Research Group Molecular Botany. the microscope. The doctoral candida- Just 90 seconds later, the algae are mo- A rapid change in the concentration of te from India, who came to Jena to do tionless and when one looks more close- calcium ions is a common alarm signal his Master’s degree in Molecular Life ly, one can see that their flagella have for many cell types, which regulates a Sciences, examines the species Chlamy- fallen off. large number of metabolic pathways. domonas reinhardtii on a microscope sli- »To be able to observe the change in de. The oval-shaped microalgae, a good The Jena researchers have discovered the level of calcium in the cell, we in- 10 micrometres in size, have two flagella why these bacteria have such a devasta- troduced the gene for a photoprotein with which they busily swim around— ting effect on the green algae. It seems into the green algae, which causes lumi- that is, until Prasad Aiyar uses a pipette that a chemical substance plays a central nescence if the calcium level increases. to add a drop of a bacterial solution. The role in the process, as the teams under This enables us to measure the amount

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Chlamydomonas reinhardtii

Tiny, nimble and quick: the single-celled green alga Chlamydomonas reinhardtii measures just 10 micrometres—a good 10 times thinner than a sheet of paper. But with their two flagella, these algae can really speed up. Taking its size into account, C. reinhardtii swims as much as 12 times faster than a human being. This tiny alga is usually in a hurry because of changes in the light. Depending on the incidence and intensity of the light, it seeks out the best position for photo- synthesis and energy generation. These microalgae live in fresh water all over the world and, in addition to bodies of water, they also occur in damp soil. physiology. As the green alga only has a haploid (single) chromosome set, To perceive light, C. reinhardtii uses a large number of photoreceptors. Some targeted manipulations of the microalga’s genetic material can be imme- of these are located in what is called the eyespot, which is on the »equator« diately studied. C. reinhardtii was one of the first green algae for which the of the single-celled organism and is coloured orange by carotenoids. Work on genome was fully sequenced, which underlines its importance as a model these receptors has opened up a new field of research—optogenetics—in which organism. Its genetic material comprises more than 15,000 genes, some of particular proteins from Chlamydomonas are put to use in neurobiology as »mo- which correspond to plant genes, while others show similarities with animal lecular light switches«. genes.

The alga has a pronounced day-night rhythm, which is controlled by an »internal What is more, the green alga is increasingly important for biotechnological clock«, similar to the way this operates in humans. Even if the algae are kept processes. For example, it is used to produce biodiesel or alternative ener- in the dark for an extended time period, this rhythm continues to work, with a gy sources such as hydrogen. C. reinhardtii is also the first plant organism period of around 24 hours, which means that the algae »know« when it is actu- that is known to digest cellulose, i.e. other plants, in order to generate ener- ally day or night. Chronobiologists call this a circadian rhythm and distinguish gy. If its environment contains too little carbon dioxide, which it needs for between a subjective day and a subjective night. If the green algae register light photosynthesis, the microalga forms enzymes that enable it to break down pulses during their subjective day, they swim towards the light. If light pulses are cellulose instead. This makes the alga an interesting organism for the ge- shone on them during their subjective night, however, they do not react. neration of biofuels from plant waste containing cellulose.

C. reinhardtii is also interesting for research because this simple organism can As early as 2014, the phycology section of the German Botanical Society be used to study many fundamental processes of developmental biology and named Chlamydomonas reinhardtii »alga of the year«.

Doctoral candidate Prasad Aiyar studies cultures of the single-celled green alga Chlamydomonas reinhardtii. SCHWERPUNKTFEATURE 35

Research team head by Prof. Dr Maria Mittag (back row left) and Dr Severin Sasso (back row right): David Carrasco Flores, Dr María García-Altares (HKI), Prasad Aiyar und Daniel Schaeme (front row from left).

of calcium with the help of the lumines- communication between algae and bac- life—not least for human beings—de- cence,« explains Prof. Mittag, Professor teria. Numerous research groups have pend on them, for example food or air. for General Botany. In some cases, the dedicated their efforts to studying the changes in the calcium lead to changes »chemical language« between microor- This is also true of microalgae such as in the direction of movement, for ex- ganisms and their environment as part Chlamydomonas reinhardtii. Such photo- ample after light perception. In other of the Collaborative Research Centre synthetic microorganisms (phytoplank- cases, for example after the bacterial at- »ChemBioSys«. Microbial species com- ton) make a contribution of about 50 per tack, they cause the loss of the flagella. munities occur in virtually every habitat cent towards fixing the greenhouse gas on Earth. »In these communities, both carbon dioxide and, as a byproduct of the species composition and the inter- photosynthesis, they supply the oxygen Researching the »chemical language« relations between individual organisms that is essential for our survival. between microorganisms and their of one or more species are regulated by In addition, microalgae, which are environment chemical mediators,« says Prof. Hert- found in fresh water, wet soils or the weck, who is the speaker for the Collab- world’s seas and oceans, represent In addition, the teams were able to show orative Research Centre and head of the an important basis for food chains, that the bacteria can tap the algae and Biomolecular Chemistry department at especially in aquatic systems. For exam- use them as a nutrient source if they HKI. ple, zooplankton in the oceans feed on are lacking in nutrients. »We have evi- The aim of the interdisciplinary research the algae and together they provide food dence that other substances from the partnership is to explain the fundamen- for crustaceans, which in turn are eaten toxic cocktail released by the bacteria tal control mechanisms in complex bio- by fish, before these are eaten by bigger also play a role in this,« says Maria Mit- systems, which affect the whole of life fish or caught by humans. »In view of tag. Her team, once again in coopera- on Earth. »We want to understand the the huge significance of microalgae for tion with the teams of Prof. Hertweck mechanisms through which the micro- human life, we still know astonishingly und Dr Sasso, now also wants to track bial community structures are formed little about the fundamental elements down these substances, in order to gain and their diversity maintained.« They and the interactions in their microscopic a precise understanding of this chemical are important, because essentials of world,« says Prof. Mittag.

Original Publication Contact Phone: +49 36 41 9-49 201 Antagonistic bacteria disrupt calcium Prof. Dr Maria Mittag, Dr Severin Sasso +49 36 41 9-49 475 homeostasis and immobilize algal cells. Matthias Schleiden Institute of Genetics, Email: [email protected] Nature Communications (2017), Bio­informatics and Molecular Botany [email protected] DOI: 10.1038/s41467-017-01547-8 Am Planetarium 1, D-07743 Jena, Germany www.botanik.uni-jena.de

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Entrance to the subsur- face: groundwater study site in the Hainich Natio- nal Park in Thuringia. SCHWERPUNKT 37

Surviving in the subsurface

The world beneath our feet is full of life, with a multitude of microorganisms constantly busy in the soils and sediments, in groundwater and even in the rocks. But life is hard underground, lacking in almost everything that organisms need in order to live: nutrients, light and energy sources. Moreover, the depths are exposed to extreme temperatures and high pressure. To date, very little research has been done on the microbes that brave such an inhos ­pitable environment and the strategies they use to survive there. Ecologists, geoscientists and chemists from Jena are follow- ing the traces of this hidden life underground.

BY UTE SCHÖNFELDER Measuring tube of a groundwater well, used for va- rious purposes, such as taking groundwater samples, monitoring probes or on-site experiments.

There is a saying that necessity is the nected survival network makes the ter aquifers. »The boreholes go down mother of invention. When people lack ecosystem in groundwater aquifers ex- nearly 100 metres through soil and rock food or other necessities of life, they are tremely vulnerable, says Prof. Küsel. »If layers from the quaternary period and more willing to share, exchange and one species suffers damage or becomes the Upper Muschelkalk,« says Prof. Kai improvise. Things are no different in extinct, its partners are also impacted.« Uwe Totsche, hydrologist and coordina- the microscopic world underground, How this subsurface microbial balance tor of AquaDiva alongside Prof. Küsel for example in groundwater. Deep in is maintained, how it arises in the first and Prof. Susan Trumbore. the rocks, where rainwater accumulates place, and what influences it, are all to- In this way, the researchers were able after seeping through the soil, microor- pics being investigated by researchers to use the drill cores to reconstruct the ganisms cannot expect to live the high from Jena, together with numerous soils and the geological underground life. If they want to survive on the scar- partners, as part of the Collaborative of this outdoor laboratory. In addition, ce supply of nutrients down below, far Research Centre (CRC) 1076 »AquaDi- the water and rock samples obtained are from the metabolic cycles above ground, va« (see p. 11) now also providing remarkable data on they need reliable partners. the microbial communities in the sub­ To this end, they have established a surface. unique research platform in the Hainich Live reduced to the bare minimum National Park in the German state of Thuringia: the Hainich Critical Zone Ex- »Astonishing« single-cell organisms »There is a whole range of microorga- ploratory (CZE). In this open-air labora- »washed« from soils into the ground- nisms that have made their home in tory of more than 12 square kilometres, water groundwater,« says Prof. Kirsten Küsel. the researchers take samples of water, The lives of bacteria and other single-cell gas and other materials from under- In a current publication, for example, organisms here are reduced to the bare ground compartments, soils, the unsa- the research team characterises the bio- minimum. »Most of these organisms turated zone, and the groundwater, in diversity of what are called Archaea in have extremely reduced genomes and order to understand their characteristics groundwater and rock. These primeval depend on partners for their survival,« and functions. single-cell organisms frequently colo- according to the ecologist. In order to The area known as the »Critical Zone« nise habitats with extreme conditions. save energy, many microbes have sim- extends from the near-surface atmo- We know of Archaea that live at tempe- ply »shut down« or »done away with« sphere down to the bottom of ground- ratures of over 100 degrees Celsius, for some of their metabolic path­ways and water aquifers. A large number of example in geysers in areas of volcanic maintain only the most basic emergency measuring and sampling sites have activity. Others can withstand extremely programme. This helps them survive, been set up over a six-kilometre tran- high pressure or high salt concentrati- but it means that they need metabolites sect in the Hainich CZE. Starting in the ons. But substantial numbers of Archaea from other organisms that have opted forests of the Hainich National Park, also occur in the soil. for a different energy-saving strategy, across pasture and further on to crop- The current Jena-based study shows that so that they can exchange substances es- land, the researchers have drilled into the Archaea living in the soil find their sential to life. Such a precisely intercon- the ground down to the groundwa- way into the groundwater when water

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BACKGROUND

Scientists today mainly use the methodology of genome sequence analysis to identify microorganisms in soil or water samples. Compared with earlier me- thods, such as culturing microbes on growth media, this has the advantage that one can also analyse organisms which it has not been possible to culture to date. In addition, the high-throughput technique provides results very quickly and is much less labour-intensive. Photo above: drilling core from a Schillkalk bench (Upper Muschelkalk). The fissures widened by karsti- A »genetic fingerprint« of the microbes is used for identification. As with an ac- fication represent groundwater flow paths. tual fingerprint, it can be compared with the other samples and in this way, orga- Photo right: sampling groundwater in the »Hainich nisms that are already known can be clearly identified. However, this technique Critical Zone Exploratory« at a location used as additionally enables researchers to identify previously completely unknown pastureland. species and determine their relationships.

In the first step of the procedure, the DNA is extracted from the microorganisms found in the water or rock samples. Great care must be taken in doing this, to avoid contamination with other microorganisms present everywhere in our en- vironment. The DNA fragments thus obtained—usually very few in number—are and materials are transported from the subsequently copied in large numbers using the »Polymerase Chain Reaction soil through the underlying rock strata. (PCR)« method. The genetic information is then »read out«, which means that »The microbiomes in the forest soil and the DNA is sequenced. groundwater are usually totally differ- ent worlds,« notes Prof. Küsel. These Among other things, what is known as 16S rRNA is of interest in identifying microorganisms are significantly differ- microorganisms. This denotes segments of ribosomal RNA (rRNA) that are pre- ent in the way they live. The professor sent in all organisms and are preserved throughout evolution. The ribosomes for Aquatic Geomicrobiology adds: are complex structures made of nucleic acids and proteins, which occur in all »Therefore, when we find soil-dwelling cells and on which protein biosynthesis takes place—a universal process of life. organisms in groundwater, it is no coin- The 16S rRNA gene is highly conserved, which means that it is present in all cidence.« She cites the fact that surface organisms, but it is also characterised by very high variability. In publicly ac- organisms enter the groundwater as evi- cessible databases, there are now thousands of sequences of 16S rRNA genes dence for the close connection between available as reference sequences, which enable immediate identification. habitats above and below ground. Although most Archaea from the soil This method is not only used for analysing environmental samples. It is current- do not survive long in water, the re- ly applied virtually everywhere that microorganisms need to be identified, for searchers have found evidence of Ar- example for detecting pathogens in clinical diagnostics. chaea in groundwater samples over the entire transect. According to them, this Knowledge of 16S rRNA provides not only the basis for detecting a specific shows that the microorganisms must microorganism in a sample. As this ribosomal RNA has barely changed in the enter the groundwater along the whole course of evolution, it is also a kind of »molecular clock«. It enables researchers transect. »Above all in the Hainich area, to classify each species in the universal tree of life and identify the most closely where the groundwater aquifers are re- related species. latively close to the surface, there were large numbers of the microorganisms With the aid of the ribosomal RNA gene sequences, the currently generally ac- in the water,« says Küsel. The organ- cepted phylogenetic tree has also been created. This divides the organisms isms that are most likely to survive their living on Earth into three domains: Bacteria, Archaea and Eukarya—to which all move from the soil into the groundwa- the higher organisms such as plants, animals and fungi belong, among others. ter were identified as »Thaumaarchaeo- As far as microorganisms are concerned, it is currently estimated that only one ta« (from the Ancient Greek »thauma«, to five per cent of all species are known to date. For more than 90 per cent of all meaning »miracle«) and »Woesearcha- Bacteria and Archaea, we only know their rRNA sequences, without ever having eota«, named after the US microbiolo- cultured them in a petri dish or having made them visible under a microscope. gist Carl Richard Woese. SCHWERPUNKT 39

In a further study, the scientists inves- of various microorganisms. »What we However, there were similarities to tigated the drill cores obtained from have discovered is that the microbial organisms discovered during the IN- the CZE to look specifically at the communities are linked to the permea- FLUINS research drilling project in the microorganisms living in them. Micro- bility of the rock and therefore appear Thuringian Basin. »These were samples biologists and geoscientists from the to depend on the rock’s cavity struc- from the same geological layer that we teams of Prof. Küsel and Prof. Totsche ture,« says Prof. Küsel. »This controls sampled in the Hainich,« says Totsche. took small rock samples from the co- the length of contact between water and For this reason, it is conceivable that the res, which were examined for traces of the rock matrix, and thus determines organisms have the same origin—but microbial DNA contained within them the living conditions in the ecological this theory will have to be supported by (see also box on p. 38). niches,« explains Prof. Totsche. Areas future research. What is certain is that of high permeability, where the water the calcareous limestone rocks are over flows relatively quickly, are home to or- 230 million years old and were formed Signs of life from ancient rocks ganisms that are different from those in from sediments from the seabed. »This areas of limited permeability. Further- soil, too, once teemed with life,« says It was discovered that signs of life were more, the organisms found in the rock Kirsten Küsel. »It is possible that the also present in the rocks itself: in the samples differed from those in compa- microbes from the rock are descendants finely crushed rock samples, researchers rative samples from groundwater or of these ancient organisms of 230 mil- indeed found the genetic fingerprints soil. lion years ago.«

Original Publications Contact

Archaeal diversity and CO2 fixers [...]. Prof. Dr Kirsten Küsel Prof. Dr Kai Uwe Totsche Archaea 2017 DOI: 10.1155/2017/2136287 Institute of Biodiversity Institute for Geosciences Aquifer configuration and geostructural Dornburger Straße 159, D-07743 Jena Burgweg 11, 07743 Jena, Germany links control the groundwater quality [...]. Phone: +49 36 41 9-49 461 Phone: +49 36 41 9-48 651 Hydrology and Earth System Science 2017 Email: [email protected] Email: [email protected] DOI: 10.5194/hess-2016-374 www.geomicrobiology.de www.hydro.uni-jena.de

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Rocks and microbes

Rock formation is generally consid- For a long time, geosciences and biology were seen as separate ered to be a geological process, in which disciplines, one focusing on the abiotic world of rocks and minerals biological processes barely play a role. It and the other on the living world. However, it has gradually become has become clear, however, that microor- apparent that the two disciplines have more in common than pre- ganisms can also form minerals such as viously thought. Microbiologists from the University of Jena, for calcite (calcium carbonate) in freshwater springs. This mineral is present in many example, are studying how bacteria form minerals and how fungi types of rock, for example in travertine break down rocks. (see box p. 43). Carbonate is normally precipitated when cold groundwater

BY SEBASTIAN HOLLSTEIN reaches the surface and becomes warm- er there. With the help of microbial processes, carbon dioxide and calcium SCHWERPUNKTFEATURE 41

PhD student Hanka Brangsch from the Institute of Microbiology inspects bacterials cultures growing with heavy metals.

sisting of calcium carbonate, or calcite, ing connection: when extrapolated to form. If the pH is low (i.e. under acidic one year’s worth of formation, the new conditions), the carbonate remains dis- minerals total around two grams per solved in the water. However, the scien- litre, which closely matches the annual tists from the Institute of Microbiology growth of a stalactite. The process that in Jena made the surprising discovery has been observed is therefore already that even in an acidic environment, bac- known from nature. teria ensure that carbonates are precipi- The current results raise many new tated instead of being dissolved. Thus, questions related to biomineralisation, the role of microorganisms in minerali- which researchers want to answer in the sation may have to be re-evaluated. years to come. »Our aim is to identify the process behind this mineralisation,« says Erika Kothe. »With one bacterial Do bacteria secrete minerals? strain—a streptomycete—we have be- gun to switch off genes in order to find »At the calcareous sites near Bad Kö- the genetic basis responsible for mineral sen, we took samples of various bacte- formation. We have already obtained rial strains from the groundwater, rocks promising initial results.« and soil, and then investigated whether Applied research is already drawing on they could also achieve biomineralisa- the fundamental processes of this min- tion under laboratory conditions,« says eral formation: the information can, for Prof. Erika Kothe. »More than 92 per example, advance the development of cent of microorganisms do indeed form self-repairing concrete. Spores could be carbonates, usually calcite, and in rare integrated into concrete or road surfa- cases also calcite containing magnesium ces, which, when water entered, would or vaterite.« Approximately a third of germinate and start to induce minerali- them created an alkaline environment sation that would seal the cracks from in the process, while most others had no the inside. influence on the pH of the surrounding medium. Six strains even produced For Erika Kothe, the results demonstra- acidic conditions. »The process by te once again the benefits of cooperati- which the formation of minerals at a on between microbiologists and geo- low pH is achieved is so far unknown,« scientists. »We now know that min-eral explains Kothe. formation is far more complex than we When they examined individual bacte- thought, and that microbiological pro- ria more closely, the researchers noticed cesses play a key role in it.« This would that it was not essential for the newly bring the two disciplines even closer to- created minerals to be deposited di- gether. eventually bind to form calcite. In this rectly on the bacterial cells; they also At Friedrich Schiller University (FSU) in process, called »biomineralisation«, occurred at a distance from the cells. Jena, this is already happening. Coope- bacteria cause solid carbonate to preci- This means that there must be a diffu- rative research initiatives have existed pitate, forming small crystals of various sion mechanism at work, which trig- since 2000, and in 2005 these resulted shapes, which settle as sediment in wa- gers the mineralization, and substances in a BSc/MSc degree programme in ter, referred to as sinter rocks. It had pre- secreted by the bacteria probably play Biogeosciences. Since 2006, young rese- viously been assumed that the pH value a role. In addition, the external form of archers have been working together in of the environment was the driving the precipitate varies. »We have found the »Jena School for Microbial Commu- force for this process and that that this very different morphologies of the crys- nication« (JSMC), which has been fun- was how microbes could influence the tals, from round through elongated to ded by the Excellence Initiative of the mineralisation process. When the pH is rosette-shaped,« says microbiologist German Federal Ministry of Education high (i.e. under alkaline conditions), car- Kothe. And the microbiologists in Jena and Research and the German Research bonate precipitates and sinter rocks con- have also discovered one more astound- Foundation. In varied interdiscipli-

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Historical photograph from 2005: point cone mine dump in Paitzdorf near Ronneburg in the former uranium mining area of Wismut. The mining landscape in eastern Thuringia has since been comprehensively reclaimed and regreened.

nary projects within this initiative, re- searchers are uncovering the means by which microorganisms influence many different areas of life. In one example, the biogeoscientists are developing me- thods for remediating metal contamina- tion at mining sites all over Europe, thus allowing the land of former heap sites to be reused. Another new research re- sult offers a promising approach to this problem.

Fungi »nibble« on rocks

Here again, the biological version of a phenomenon known principally from the geosciences plays a major role. This time, the focus is not on the creation of rock, but rather the opposite—weather- ing. It is not only the effects of weather and physical processes that break down rocks: organisms also play a part in weathering. The FSU researchers have now found that fungi can attack rock and, in the process, dissolve heav- y metals from this hard material.

»If one brings ground rock into con- tact with these fungi, metals can be re- leased—we already knew that,« says Erika Kothe. »For this reason, we want- ed to investigate more closely whether this was also possible in the case of compact rock samples.« The micro- biologists suspected that the enzyme laccase plays a decisive role here. This protein is found mainly in wood-rot- ting white-rot fungi, which need it in order to break down lignin, a biopoly- mer present in wood that can only be completely broken down by fungi. For this reason, the researchers grew such a fungus, with the Latin name Schizophyllum commune (see box on the right), on black slate slabs in the labo- ratory. The rock material from the spo- il tip of the tourist mine Morassina or from the former uranium mining area near Ronneburg in Thuringia was then analysed after incubation with the fun- gus. »We observed that Schizophyllum SCHWERPUNKTFEATURE 43

Calcite crystal on mineral realgar from China (mineralogical collection of the University Jena).

BACKGROUND

The mineral calcite consists of calcium car- penetrated the rock and formed etch bonate. It is usually a colourless mineral, pits under the growing fungal hyphae which dissolves with carbon dioxide emis- to a depth of approximately 200 nano- sion in an acidic environment. Characteristic metres,« explains Kothe. »Black slate is for calcite crystals is their birefringence: rich in organic material, which is used incident light is split into two rays of light by the fungus for nutrition.« with different refractive indices. Calcite is a rock-forming mineral and it occurs, for ex- To establish which factor is ultimately ample, in marble and limestone. Stalactites decisive for this behaviour, the re- and stalagmites in caves may also consist searchers switched off individual of calcite. genes of the fungus. After knocking out the gene responsible for the forma- Vaterite, which is chemically related to calci- The rock called travertine consists mainly of cal- tion of laccase, they obtained confirma- te, also consists of calcium carbonate, but cite (calcium carbonate), which precipitates as tion of their hypothesis. differs from calcite in its crystalline structure. »fresh-water limestone« from warm or cold springs. Furthermore, they discovered that As a result, the significantly rarer vaterite has Well-known features are, for example, the »travertine Schizophyllum commune produces a par- different characteristics: it forms only small, terraces« in Pamukkale, Turkey, or in Mammoth Hot ticularly large amount of the enzyme filamentous crystals and is harder to dissol- Springs, Yellowstone National Park, USA. The rock when grown with the rock material ve than calcite. Vaterite forms in mineral-rich is light in colour, usually yellowish and brown, and present—probably because it needs springs and also in organic tissue. It is a con- has a porous structure. Travertine is used as build- more of this enzyme in order to gain stituent part of gallstones and kidney stones, ing material, for example in many historical struc- access to its food source. for example. tures such as churches.

These findings might help to develop The fungus Schizophyllum commune (split gill fun- new methods for reclaiming land that gus) is widespread and found all over the world. has been mined. By breaking down the Especially interesting is the fact that this fungus organic material in the rock, the fun- forms more than 20,000 different »sexes« or mating gus dissolves the heavy metals embed- types, enhancing the probability of reproducing sex- ded in it. These metals are thus con- ually with outbreeding, and limiting inbreeding ge- centrated in the water. With the help of netically. It occurs as a typical cause of white rot on the fungus, such heavy metal residues deciduous and coniferous trees. could therefore be removed biologi- cally. »This shows us yet again the po- Schizophyllum commune produces fruiting bodies on tential of microorganisms,« says Erika dead wood, but also in petri dishes. Along with other Kothe, »and we will continue with our fungi, it appears in the special exhibition, »Dem Ge- ruch auf der Spur—Die chemische Sprache der Natur« research on these interactions between (Following the scent—nature’s chemical language), biosphere and geosphere in the future, in the Phyletic Museum of the University Jena until together with our colleagues from autumn 2018. Geosciences.«

Original Publications Stone-Eating Fungi [...]. Advances in Applied Microbiology (2017), DOI: 10.1016/ bs.aambs.2017.01.002; Calcium carbonates: Contact Induced biomineralization with controlled Prof. Dr Erika Kothe Phone: +49 36 41 9-49 291 macromorphology. Biogeosciences (2017), Institute of Microbiology Email: [email protected] DOI: 10.5194/bg-2017-251 Neugasse 25, D-07743 Jena, Germany www.mikrobiologie.uni-jena.de

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Imaging with »X-ray vision«

With ultrashort X-ray pulses, processes and structures can be resolved down to the nanometre range. X-ray pulses are usually generated in huge particle accelerators, such as the DESY in Hamburg. But the access to such facilities is limited and their operation is extremely expensive. Physicists in Jena are therefore developing »handy« laser systems, which enable ultrashort X-ray pulses at laboratory scale and thus allow a wide variety of applications in the lab.

BY SEBASTIAN HOLLSTEIN

A visit to the optometrist often involves research facilities, but they have now optical coherence tomography. This found a possibility for applying it at a imaging process uses infrared radiation smaller scale. to penetrate the layers of the retina and In this approach, they focus an examine it more closely in three dimen- ultrashort, very intense infrared laser in sions, without having to touch the eye a noble gas, for example argon or neon. at all. This allows eye specialists to diag- »The electrons in the gas are accelerated nose diseases such as glaucoma without by means of an ionisation process,« ex- any physical intervention. plains Fuchs. »They then emit the XUV radiation.« It is true that this method is However, this method would have even very inefficient, as only a millionth part greater potential for science if shorter of the laser radiation is actually trans- wavelengths were used, thus allowing formed from infrared into the extreme a higher resolution of the image. Phy- ultraviolet range, but this loss can be sicists at Friedrich Schiller University offset by the use of very powerful laser Jena have achieved just that and they sources. »It’s a simple calculation: the have reported their research findings in more we put in, the more we get out,« the specialist journal »Optica«. adds Fuchs.

First XUV coherence tomography at The generation and application of ultraviolet Strong image contrasts are produced laboratory scale radiation has become a key topic at a num- ber of research institutes in Jena. Physics The advantage of XUV coherence tomo- doctoral candidate Robert Klas can be seen For the first time, the University phy- here behind such a test setup. He and his graphy is that, in addition to the very sicists used extreme ultraviolet radia- colleagues in the team led by Prof. Jens high resolution, the radiation interacts tion (XUV) for this process, which was Limpert focus laser pulses in a birefringent strongly with the sample, because dif- generated in their own laboratory, and crystal, which doubles the frequency of ferrent substances react differently they were thus able to perform the first the original infrared light. As a result, laser to light. Some absorb more light and pulses in the green wavelength range are XUV coherence tomography at lab- generated. In a second step in what is called others less. This produces strong con- oratory scale. This radiation has a wa- cascaded frequency conversion, these trasts in the images, which provide the velength of between 20 and 40 nanome- pulses are focused again, resulting in pulses researchers with important information, tres—from which it is therefore just a of an even higher frequency in the extreme for example regarding the material com- small step to the X-ray range. ultraviolet range (XUV). Limpert and his position of the object being examined. team are leaders in, among other things, the »Large-scale equipment, that is to say development of ultrashort pulse lasers with »For example, we have created three- particle accelerators such as the German a very high medium-range performance, dimensional images of silicon chips, in Elektronen-Synchotron in Hamburg, are which can then be used to produce intensive a non-destructive way, on which we can usually necessary for generating XUV XUV radiation. distinguish the substrate clearly from radiation,« says Silvio Fuchs of the Insti- structures consisting of other materi- tute of Optics and Quantum Electronics als,« adds Silvio Fuchs. »If this procedu- of the Jena University. »This makes such re were applied in biology—for investi- a research method very complex and gating cells, for example, which is one costly, and only available to a few re- of our aims—it would not be necessary searchers.« The physicists have alread- to colour samples, as is normal practice y demonstrated this method at large in other high-resolution microscopy me- SCHWERPUNKT 45

From right: Prof. Gerhard G. Paulus, Silvio Fuchs, Martin Wünsche and Dr Christian Rödel by a laser-driven X-ray source. The physicists want to make it possible to use X-ray pulses for new imaging procedures, for example for studying cells.

thods. Elements such as carbon, oxygen for producing images of small struc- that it is possible to use this method at and nitrogen would themselves provide tures, for example in semiconductors, laboratory scale.« the contrast.« the structure sizes of current chips are The long-term aim could ultimately be Before that is possible, however, the in some cases already smaller. However, to develop a cost-effective and user- physicists of the University of Jena still with new, even more powerful lasers, it friendly device combining the laser with have some work to do. »With the light should be possible in future to achieve the microscope, which would enable the sources we have at the moment, we can a depth resolution of as little as three semiconductor industry or biological la- achieve a depth resolution down to 24 nanometres with this method,« notes boratories to use this imaging technique nanometres. Although this is sufficient Fuchs. »We have shown in principle with ease.

Original Publication Contact Phone:+49 36 41 9-47 615 Optical coherence tomography with nano­ Silvio Fuchs +49 36 41 9-47 201 scale axial resolution using a laser-driven Prof. Dr Gerhard G. Paulus Email: [email protected] high-harmonic source. Optica (2017), Institute of Optics and Quantum Electronics [email protected] DOI: 10.1364/OPTICA.4.000903 Max-Wien-Platz 1, D-07743 Jena, Germany www.ioq.uni-jena.de

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GPS for antibiotics

How does an active substance know where it should go? And how does the substance get from the bloodstream to exactly the right spot? Using polymer-based nanosystems, researchers in Jena want in future to direct drugs in a targeted fashion to the source of the infection and deliver active substances—antibiotics, for example—precisely where they are needed.

INTERVIEW: AXEL BURCHARDT Chemist and materials scientist Prof. Dr Ulrich S. Schubert is coordinator of the Collaborative Research Centre (CRC) 1278 »PolyTarget« (see also box p. 11). With innovative carrier materials for the targeted application of medicines, the research consortium supports the diverse and broad-based sepsis and infection research being carried out at the University of Jena, Jena University Hospital and non-university research institutes in Jena.

You are an expert in innovative polymer-based batteries, tainer is going and further optimise its path. The CRC is first self-healing materials and innovative applications of inkjet of all a basic research project, with which we want to develop printing. Why are you and your team of chemists and mate- an understanding of the size, the load and the type of polymer rial scientists now also developing new drugs? we need to use in order to deliver genetic material or an anti- Another of our specialist fields is that of pharmaceutical po- biotic or peptide to the desired location. Our aim is to develop lymers, which are synthetic materials for use in medicine. To- a platform that will also make it possible in future to develop gether with a strong University Hospital and the non-univer- new drugs in a relatively short time to the stage where they sity institutes, we have been able to build up a solid position, can be used to cure other diseases. which is reflected in the new Collaborative Research Centre »PolyTarget«, funded by the German Research Foundation. In Up to now, you have never limited yourself to basic research. this CRC, we want to package active substances in such a way Are you also planning to put the nanocontainers to practical that they can be sent directly to the location of the disease, use in therapies and diagnostics? without side effects. That is of course also planned. We already have a spin-off, SmartDyeLivery GmbH, which, in collaboration with the Uni- Why should active substances be packaged in nanoparti- versity Hospital, will shortly be working with a large animal cles and why are these particles in particular well-suited for model on a very specific pathology—sepsis-induced choles- tackling infectious diseases? tasis. At the same time, there are various application-oriented There are many well-known antibiotics which cannot be projects in collaboration with industry. used, because they have too many side effects: the dose is too high and the drugs are distributed throughout the body. When can we hope to see the first polymer nanocontainers And there are many potential new antibiotics which cannot in use? be used, because they are not water-soluble and therefore That will depend on how much time is needed for the medical not bioavailable. We offer solutions for both of these limita- formalities and the studies. The goal of the CRC is in any case tions. We package the active substances in tiny polymer-based to achieve some translation into practice within four years, so nanoparticles. This causes far fewer side effects, partly becau- that follow-up projects can be carried out directly with com- se the doses can be smaller, as we ensure that they are taken panies. up specifically by the organs and cells that are targeted. We are developing these new pharmaceutical polymers using ro- The field is so huge—is it possible to deal with it, even with botics, with high-throughput methods, working together with such a diverse team? our medical colleagues right up to the application stage. Naturally, we have restricted our work. We use the nano- medicine that we want to pursue really only for infection- Your nanoparticles are containers for these active substances. related diseases, such as sepsis. Because here in Jena we have a What does the ideal container for such substances look like? strong position in this field, with the other priority areas at the The ideal container for an active substance is of course non- University and the non-university institutes. Only together toxic and biodegradable, and all its harmless components can we achieve critical mass. But in Jena we are lucky to have, should ultimately be excreted. Furthermore, it has a GPS sys- among other disciplines, Medicine, Pharmaceutics, Bioche- tem with which we can determine which organ and which cell mistry, Macromolecular Chemistry, and Material Science. the container must reach. The container also contains a dye, so There are not many locations that can offer so much in one that with a modern microscope, one can trace where the con- place. Rubrik 47

Calendar: The myth of the October Revolution

Hundred years ago, on 25 October 1917, the Bolsheviks took over the reigns from the Provisional Government in Russia. The upheaval at the Winter Palace turned to a glorification of the Great October Socialist Revolution which was illustrated accordingly later. It is a myth that has endured to the present day.

BY STEPHAN LAUDIEN

The shot fired from the armoured cruiser Aurora (»red sky at morning«) was the signal for the storm on the Winter Palace and heralded the new era of Communism at the same time. Thousands of Bolsheviks attacked the hated palace of the Rus- sian tsars in Saint Petersburg and gained the victory—a strong signal for the workers in the whole world. What a story! Well, it is not a true one. »From its beginnings, the October Revolution was a myth arranged as such,« says the historian specialized in the East European history Prof. Dr Jörg Ganzenmüller. According to him, the term »revolu- tion« itself is not tenable. In 1917, there were no revolutionary masses on the streets. It was rather a concentrated action in which the Provisional Government was arrested and strategic points in Saint Petersburg were occupied. Jörg Ganzenmüller describes it as an overthrow. In spite of this, the myth of the Great October Revolution lives on, even hundreds years later. It is the images of the events to be blamed for it, to be more accurate, those missing. The people already rose in February 1917. The reason for the revolution was a provision crisis in the Russian Empire which had been due to the World War I. After the tsar Nicholas II. had been forced to abdicate, the power was shared by the Provi- sional Government and the soviets, i.e. workers’ and soldiers’ councils. Since the Provisional Government kept fighting in the unpopular war, Lenin and his Bolsheviks seized its power.

The vast majority of images originate in a film by Eisenstein

»The Bolsheviks had been enjoying the support among work- ers and soldiers,« explains Jörg Ganzenmüller. In the Constitu- ent Assembly elections of 1918, they thus received 25 percent of votes. In the October Revolution, however, the masses were A bust of Vladimir Ilyich Ulyanov, alias Lenin. The October »Revolution« he led was not involved. Later on, the event was therefore arranged ac- rather an overthrow than a revolution. To the present day, false images have been cordingly. Apart from the events on the historic sites on the circulating about the event. anniversaries, the images were provided by the film October: Ten Days That Shook the World by Sergei Eisenstein from 1927 primarily. In vast majority, the images of event, which we still ticularly the Mensheviks who had been defeated in the elec- have in mind, originate in this film. As Jörg Ganzenmüller tion. Having a great power, the myth of the storm on the Win- comments, the Bolsheviks aimed at suggesting to posterity ter Palace made its way to German textbooks, too. Whereas in that the masses had been on their side. As a matter of fact, in East Germany the Soviet interpretation was adopted, in West 1918 the majority of population voted for the Socialist Revolu- Germany one could find »images« of the October Revolution tionary Party—agrarian socialists popular with the peasants. even in the nineties—despite the fact that none exist. Up until »After the Bolsheviks had won the civil war, they wanted to today, documentaries have been trying to replace the missing be seen as the revolutionary force,« says Prof. Ganzenmüller. images by film clips, especially from the one by Eisenstein. At the same time, the competitive socialist parties should have But only a few of them refer to the source—enabling the myth been marginalized—apart from the social revolutionists, par- to endure.

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MEDICINE

Surviving with leukaemia

Targeted therapy for chronic myelogenous leukaemia (CML) continues to be effective and to have few side effects, even over a period of 11 years. This was the result obtained by a team led by Jena haematologist Prof. Andreas Hochhaus in a fresh analysis of the IRIS study. This pioneering clinical trial underpinned the effectiveness of targeted therapy for CML and the accompanying molecular monitoring.

BY UTA VON DER GÖNNA

Chronic myelogenous leukaemia (CML) which is close to the survival rate in the is the second most common form of general population,« says Prof. Andreas chronic leukaemia. This disease of the Hochhaus, Director of the Department haematopoietic system is caused by a of Haematology and Medical Oncology specific genetic mutation (portions of of Jena University Hospital, describing chromosomes 9 and 22 switch places) a key result of a long-term analysis of which leads to a sharp increase in the the IRIS study data. number of white blood cells. The new The study was begun in 2000 to compare active ingredient tested in this trial—a the effectiveness of the tyrosine kinase tyrosine kinase inhibitor—specifically inhibitor »Imatinib« with the standard inhibits the activation of the altered therapy of the time, which was to give protein that causes continued division, patients the immunostimulant interfe- i.e. reproduction, of the leukaemia cells. ron alpha. »IRIS« stands for »Interna- These new drugs have fundamental- tional Randomized Study of Interferon ly improved therapy for this disease, Versus STI571«. Haematologist Prof. Andreas Hochhaus and his which previously could only be cured team conducted a fresh analysis of the »IRIS« by stem-cell transplantation. The therapeutic response and the toler- study, which began in 2000. »Currently, 83 per cent of CML patients ability of »Imatinib« were so good that live for 10 years after their diagnosis, the majority of patients from the inter- Rubrik 49

Cluster of Excellence »Enlightening the Receptome: From Biophysics to Clinical Applications«

The »receptome«, the sum of all receptor molecules of an organism, makes up more than five per cent of its proteins. Through interactions with other molecules, these molecular switches direct a large number of metabolic processes. Due to their function, receptors are ideal targets for therapeutic applications. The aim of the Cluster proposal is to unravel the receptome in all its diversity and use the knowledge thus obtained to develop innovative diagnostic procedures and personalised therapies for the treatment of diseases. It is a joint proposal by the Universities of Würzburg and Jena, headed by Prof. Markus Sauer (Würzburg) and Prof. Klaus Benndorf and Prof. Christian Hübner (both in Jena).

feron group switched to the other ther- mechanisms and develop new thera- of white blood cells with the charac- apy, and »Imatinib« became the stand- peutic approaches. Specific interactions teristic mutation falls below a specific ard medication for treating this form of of proteins and signal molecules—such threshold, the disease is considered to leukaemia. The follow-up of the parti- that between »Imatinib« and the tyro- be in complete remission. cipants in the study is now providing sine kinase—are therefore the focus of valuable data relating to long-term ther- a current joint Cluster proposal by the »Recent therapy studies have shown apy. Andreas Hochhaus: »The active universities of Würzburg and Jena un- that patients in deep remission can substance is also effective when applied der the Excellence Strategy programme safely stop their therapy. This has ma- over the long term, so that patients are of the German federal government and jor consequences for their quality of life living free from CML symptoms for 10 federal states (see box above). and also for therapy costs,« notes An- years and longer. The IRIS study also dreas Hochhaus, who coordinates the showed that during this period, no criti- German CML Alliance in Jena. This is cal side effects accumulate or intensify.« Standards established for therapy and a network of university centres, outpa- monitoring tient haematology specialists and pati- Not least as a result of the experi- ent representatives. »Thanks to the fact ence gained from the IRIS study, chronic The effectiveness of a CML therapy is that the IRIS study has substantiated the myelogenous leukaemia, with its char- demonstrated by patients entering re- success of the targeted therapy in trea- acteristic mutation, has become the mission with a reduction in the propor- ting CML, we can turn our attention to model disease for the diagnosis and tion of genetically modified blood cells questions that go beyond ensuring pa- treatment of many cancers with com- still present. To determine remission, a tient survival. These concern, for exam- plex genetic causes. Findings relating quantitative molecular genetic method ple, better procedures in CML treatment to the individual tumour biology can of analysis was developed for the IRIS and the social and psychological aspects be used, for example, to make targeted study. This method is now standard of living with the disease over the long interventions in the molecular tumour for monitoring CML. If the proportion term.«

Original Publication Contact Long-Term Outcomes of Imatinib Treatment Prof. Dr Andreas Hochhaus for Chronic Myeloid Leukemia. New England Department of Haematology Phone: +49 36 41 9-32 42 01 Journal of Medicine (2017), DOI: 10.1056/ and Medical Oncology Email: [email protected] NEJMoa1609324 Am Klinikum 1, D-07747 Jena, Germany www.kim2.uniklinikum-jena.de

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Fossilised specimen of the »Bad Boy« Ponomarenkia 1 mm belmonthensis (late Permian period, Age around 250 million years).

Rolf Beutel and Dr Evgeny V. Yan of Friedrich Schiller University Jena. They have published this discovery together with renowned beetle researcher Dr John Lawrence and Australian geologist Dr Robert Beattie in the »Journal of Sys- tematic Palaeontology«. It was Beattie who discovered the only two known fossilised specimens of the beetle in for- mer marshland in Belmont, Australia.

»Beetles, which with nearly 400,000 de- scribed species today comprising almost one-third of all known organisms, still lived a rather shadowy and cryptic life in the Permian period,« explains Jena zoologist Beutel. »The fossils known to

PALEONTOLOGY date have all belonged to an ancestral beetle lineage, with species preferring narrow spaces under bark of coniferous trees. They exhibit a whole series of »Bad Boy« of the beetles primitive characteristics, such as wing cases—elytra—that had not yet become completely hardened or a body surface densely covered with small tubercles.« An international team of insect researchers has succeeded in recon- structing a long-extinct beetle with the help of a fossil. Despite being an impressive 250 million years old, Ponomarenkia belmonthensis has Earliest form of the »modern« beetle astounded researchers with its very »modern« features, which present scientists with a real taxonomic problem. In contrast, the species that has now been discovered, assigned to the newly introduced family Ponomarenkiidae, can

BY JULIANE DÖLITZSCH be identified as a »modern« beetle, in spite of its remarkable age. Modern char- acteristics are the antennae resembling a string of beads, antennal grooves, and the unusually narrow abdomen, taper- He is Australian, around half a cen- had not yet appeared on the scene, is ing to a point. What is more, unlike timetre long, fairly nondescript, 250 throwing a completely new light on the previously known Permian beetles, the million years old—and he is currently earliest developments in this group of wing cases are completely hardened, causing astonishment among both ent- insects. the body’s surface is largely smooth, omologists and palaeontologists. The The reconstruction and interpretation and the thoracic segments responsible discovery of a beetle from the late Per- of the characteristics of Ponomarenkia for locomotion show modern features, mian period, when even the dinosaurs belmonthensis was achieved by Prof. Dr notes insect palaeontologist Yan. In ad- SCHWERPUNKT 51

Insect palaeontologist Dr Evgeny V. Yan in front of the computer reconstruction of »Flat Bob«, the oldest known whirligig beetle and a contemporary of »Bad Boy«.

dition, it appears that this little beetle exoskeleton. However, the »Bad Boy« for deformations in the original fossil. had stopped living under tree bark, the ran out of luck, as there are no more tra- This allowed us to get closer to the ac- habitat favoured by its contemporaries, ces of its existence in the Mesozoic era. tual beetle,« explains Dr Yan. Based on and had adopted a much more exposed The Jena researchers dedicated the ge- precise drawings and with the help of lifestyle on plants. A significant fact is nus and family to Moscow palaeonto- a special computer program that is also that, due to its unorthodox combina- logist Prof. Alexander G. Ponomarenko. used for animation and computer ga- tion of ancestral and modern characteri- He has had a strong influence on beetle mes, a very informative 3D model was stics, this genus does not fit in any of the palaeontology for decades and super- created. »The 3D reconstruction also en- four suborders of beetles that still exist, vised Dr Evgeny V. Yan’s doctorate. It is ables us to draw conclusions about the which is why Yan and Beutel have given Yan’s elaborate reconstructions on the way the beetle moved and lived,« the it the nickname »Bad Boy«. computer that have provided the precise palaeontologist adds. He has developed »Ponomarenkia belmonthensis shows a- insights into Ponomarenkia belmonthensis. this method of visualisation, as well as bove all that the first major events of ra- the analytical process in which he also diation in the evolution of beetles took includes hypothetical ancestors of the place before the Permian-Triassic mass Informative 3D model was created beetle, since his arrival in Jena. »We have extinction,« says Rolf Beutel. Beetles as already been able to apply this process a whole survived this dramatic event, In the first stage, some 40 photographs to three newly discovered ancient beetle which saw the acidification of the seas were taken of the two specimens, which species,« Prof. Beutel is happy to report. and major volcanic eruptions, consi- were available as impressions on stone. »In this way, we have made significant derably better than most other groups »With this series of photographs an ac- steps towards deciphering the earliest of organisms—presumably because of curate 2D reconstruction was possible, stages in the evolution of an extremely their terrestrial life style and hardened with which we were able to correct successful order of animals.«

Original Publication At the dawn of the great rise: †Ponomaren- Contact kia belmonthensis [...]. Journal of Prof. Dr Rolf Beutel Phone: +49 36 41 9-49 153 Systematic Palaeontology (2017), Institute of Evolutionary Biology Email: [email protected] DOI: 10.1080/14772019.2017.1343259 Erbertstr. 1, D-07743 Jena, Germany www.speziellezoologie.uni-jena.de

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3D reconstruction of Ponomarenkia belmonthen- sis based on precise drawings of the holotype and an accurate 2D reconstruction. Due to its combination of ancient and modern characte- ristics, this genus cannot be assigned to any of the four extant suborders of beetles, which is Outliving life itself why it has the nickname »Bad Boy«.

When researchers immortalize themselves as part of the tree of life, their choice is not always a happy one

COMMENTARY BY UTE SCHÖNFELDER

Donald Trump was recently in the headlines again. »Oh, real- the Jena entomologist Rolf Beutel (see p. 50), phylogenetically ly?«, I hear you say, »so what?« After all, when does Donald classified and scientifically »christened«. Trump not cause controversy? In this case, however, it was The long-extinct insect is named after the Moscow palaeonto- not the man himself who was to blame, but a newly discover- logist Prof. Alexander G. Ponomarenko. Nothing is publicly ed species—a moth—which was named after Donald Trump known about his hairstyle. However, his work as a scientist is in early 2017. Neopalpa donaldtrumpi sports a crown of yel- obviously highly appreciated in Jena, which is why the beet- low-white scales that bears an undeniably striking similarity le—combining characteristics of both ancient and modern to the human Trump’s blow-dried hairdo. Whoever saddled species—was given the professor’s name. However, what is the poor creature with this name presumably thought it was the significance of such appreciation if a dyed-blonde pom- funny. But should the classification of species be seen as a padour is clearly just as suitable an inspiration for a name as source of jokes? academic merit? I am sure that we do not need an official body to vet names, Plants, animals and microorganisms—whether long extinct in the way that the registry office in Germany ensures that or still caught up in the treadmill of evolution—everything parents do not call their children »Darth Vader« or »Face- that walks, crawls, swims or flies, and that grows, metaboliz- book«. But please, dear taxonomists, preserve the nameless, es and reproduces is systematically classified. Thanks to the as-yet-undiscovered beetles, worms or moths from a fate like meticulous work of taxonomists, no creature goes missing—at that of Neopalpa donaldtrumpi! Be aware of the far-reaching least on paper. And if a species quits this earthly life, because consequences of your decision when you name a previously it cannot find food, a sexual partner or a habitat, or because unknown creature: you are recording it in the eternal book of climate change, an unfortunate mutation or a motorway has life. Heed the example of those who christened Ponomarenkia led to its extinction, its name and its place in the eternal tree belmonthensis! Ultimately, politics and evolution both teach us of life will endure—classified and described for all time. How that presidents and species come and go, but the scientific na- long will Neopalpa donaldtrumpi last? Or the huntsman spider mes of all beings remain. Heteropoda davidbowie, or the South American frog Hyloscirtus princecharlesi? Name your own species: if you feel called upon to give a name to a new species, get in touch with the Phyletisches Museum (Phyletic Museum). This is a question that does not arise in the case of Ponomaren- In exchange for a donation to the museum’s association, anyone can kia belmonthensis, as this beetle became extinct more than 250 choose a name for a tropical moth or butterfly species. million years ago. Nevertheless, Ponomarenkia belmonthensis For more information, please visit: has only recently been discovered by a research team led by www.phyletisches-museum.uni-jena.de/falternamen-zu-vergeben SCHWERPUNKT 53

The archaeological site in Mleiha, with recons- tructed tower-shaped tombs from the late 3rd century BCE. The site is in Sharjah, United Arab Emirates, on the Persian Gulf. Here, archaeolo- gists have found records written in Zabur, the everyday writing system of ancient Yemen.

NEAR EASTERN STUDIES

Gifts to the gods

Travelling broadens the mind, as getting to know other people and cultures makes us see our own lives in a different light. Travellers bring something back from foreign places and leave traces in those places that they have visited. Such exchanges go back thousands of years, as evidenced by the latest research results of the Jena University Semitist, associate professor Peter Stein. In the Persian Gulf area, he deciphered the inscription on a silver plaque, which is evidence that people in the Gulf region worshipped the goddess Allāt. Previously, such gifts to the gods were only known from southern Arabia—the area that is now Yemen.

BY JULIANE DÖLITZSCH

In Mleiha, an archaeological site some 55 who in recent years has been working daily matters in ancient Yemen. »Za- kilometres east of Dubai in the Emirate intensively on the written culture of an- bur was usually scratched into small of Sharjah, local researchers made two cient South Arabia, was able to solve the wooden sticks,« explains Stein. Letters, discoveries a few years ago. In excava- puzzle. With support from the Director- contracts and other official documents tions they found a small silver plaque General of the Sharjah Archaeological were written down and distributed and a handle broken off an amphora, Authority, Dr Sabah Jasim, Stein has in this way as far back as the early 1st both dating from the late 3rd century been able to study the original inscrip- century BCE. The »ancient South Ara- BCE. Both finds bear inscriptions in Ha- tions and decipher them. bian minuscule script«, as Zabur is also saitic, the language spoken in the region referred to, was previously only known 2,000 years ago. from the south of the Arabian Peninsu- However, the writing on the two objects The Zabur writing system la, but not from the Persian Gulf region. presented the researchers with a puzzle, because it did not resemble the letter What made the inscriptions initially The content of the inscriptions was also forms known from the region up to that so »unreadable« was the fact that they a source of astonishment for the re- point. Peter Stein, a researcher in Semi- were written in Zabur, in cursive letters searchers. Whereas the writing on the tic languages, cultures and histories, that were commonly used for writing handle of the amphora refers only to its

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The silver plaque from the 3rd century BCE was found at the archaeological site in Mleiha in the Persian Gulf. The text was written in Zabur, which is actually typical of the southern Arabian region. The plaque bears the inscription: »Liʿaḏḏim, the daughter of Maʿūnlāt, has offered (the goddess) Hallāt this metal plaque.« Rubrik 55

owner, the inscription on the seven-by- then brought this knowledge back home six-centimetre silver plaque is evidence with them,« says Stein. of a religious custom hitherto also un- known in the Gulf region. A second route that the Zabur script »In material and shape, the plaque re- and the religious custom might have sembles the bronze plaques that were taken runs along the south coast of typical of southern Arabia. There, they the Arabian Peninsula, through the re- were used as votive offerings to the gion Hadramawt—now the eastern part gods,« adds Stein. The letters, six to of Yemen—to Oman. Here too, people eight millimetres in size, are punched communicated using wooden sticks in- into the smooth metal surface. As was scribed with the Zabur script. »The local the usual practice in ancient South Ara- form of the ancient South Arabian wri- bia, the individual words are separated ting system that was developed in eas- by vertical lines. tern Arabia is referred to by scholars as Hasaitic,« explains Stein. The other wri- ting system we know of from the Gulf Votive offering to the goddess Allāt Region is Aramaic, which served as a lingua franca throughout the Near East Now that the content of the inscrip- from the middle of the 1st millennium tion has been deciphered, we can see BCE. An Aramaic votive inscription to clearly that the plaque was offered to the same deity on a bronze plaque was Allāt, a goddess worshipped throug- already discovered in Mleiha a consi- hout Arabia. Peter Stein suspects that derable time ago. However, it was only the goddess »might have been wors- possible to identify this votive offering Associate professor Peter Stein has deciphered the hipped here as a major goddess of the correctly against the background of the inscription on the silver plaque (photo p. 54). He is area, under the local name of Hallāt«. recently discovered silver plaque. one of the few experts in the world able to read the Starting from South Arabia, the Zabur ancient South Arabian minuscule script Zabur. script and the custom of dedicating me- tal plaques to the gods must have tra- Temples still to be discovered velled many hundreds of kilometres in order to have become a local custom at What is exciting about these votive the site in the Gulf region where it was plaques is not least the knowledge that found. This probably happened through there must have been temples or shri- trade along the famous Incense Route. nes near Mleiha. »However, apart from From numerous inscriptions found in tower-like tombs, no evidence has as Yemen, it is known that around 300 BCE yet been found for solid constructions there was lively trade between the an- in that period. The permanent settle- cient trading city of Gerrha in the east ment of the location by the previously of the Peninsula and the region that is nomadic population apparently began now Yemen. »The eastern Arabian tra- only 100 to 200 years later,« explains ders, who had not developed their own Stein. The finds do answer some ques- local written language, must have used tions, but also pose new riddles, which the South Arabian writing system and need to be solved.

Original Publication South Arabian zabur script in the Gulf: some Contact recent discoveries from Mleiha (Sharjah, Associate Prof. Dr Peter Stein Phone: +49 36 41 9-41 114 UAE). Arabian archaeology and epi­graphy Faculty of Theology Email: [email protected] (2017), DOI: 10.1111/aae.12087 Fürstengraben 6, D-07743 Jena, Germany www.theologie.uni-jena.de

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Photo left: In a laboratory at the Institute of Inorganic and Analytical Chemistry, doctoral candidate Oluseun Akintola from Nigeria shows a small glass tube containing a tiny sample of a porous polymer. The in- novative material, which demonstrates a combination of fascinating properties, opens up new possibilities in the area of switchable magnetic materials.

Photo right: Oluseun Akintola prepares a sample of the magnetic JUMP polymer for examination on a sorption-analyser. He is a doctoral candidate under Prof. Winfried Plass (in the background) at the CHEMISTRY Institute of Inorganic and Analytical Chemistry.

To attract—or not attract

in the department. The researchers have Jena chemists have developed a magnetic polymer, the »attractive« reported the material JUMP-1 in the spe- properties of which can be potentially switched on or off. The secret cialist journal »CrystEngComm« of the behind the material bearing the name »Jena University Magnetic Royal Society of Chemistry, and Prof. Polymer« (JUMP) lies in its structure: the regularly structured three- Plass’s team also designed the cover. dimensional framework is peppered with nano-pores in which various chemical molecules can be embedded, thus controlling the properties of the polymer. Three-dimensional framework with numerous cavities

BY UTE SCHÖNFELDER In addition to its appreciable interior size, the second special feature of this porous polymer is its magnetic proper- ties. »What’s more, these properties are potentially switchable, which means In the glass vessel that chemist Oluseun huge inner surface,« he says. One gram that we are currently working on che- Akintola holds up to the light, one can of the material, which fits in a teaspoon, mical modifications of the polymer see just a few small crystals. There is a has a pore surface of at least 150 square that can turn the magnetic property of violet shimmer to the fragments of pol- metres. The »Jena University Magnetic the material on or off,« explains Prof. ymer, which otherwise do not look at Polymer«—JUMP for short—has been Plass. The material consists of layers all spectacular. What is special about developed and characterised by Olu- of a two-dimensional network made them, explains Akintola—a doctoral seun Akintola, who is supported by the of magnetic cobalt clusters and orga- candidate from Nigeria working at the Evangelisches Studienwerk Villigst, as nic linkers, which are then connected department of Inorganic Chemistry part of his doctoral research under Prof. by regularly arranged bridging mo- II—is in the detail. »The crystals have a Winfried Plass, together with colleagues lecules. Plass adds: »This produces a Rubrik 57

three-dimensional crystal, the volume is that the linking molecules are re- the pores. »In this way, we can fashion of which is more than 50 per cent ca- dox-active: they can give up single elec- the polymer to fit the possible applica- vities.« Various tiny ions or molecules trons, which makes it possible to control tion,« says Plass. can be embedded in these cavities. the magnetic properties of the layers »The properties of the polymer chan- of cobalt ions. Furthermore, positively Future switchable magnetic materials ge according to the properties of these charged counter-ions can be selecti- could be used, for instance, as highly guest molecules,« says Plass. Such po- vely embedded in the overall nega- sensitive sensors for small charged rous framework substances, or MOFs tively charged polymer framework. molecules. Thanks to their appreciable (Metal-Organic Frameworks), were not These positively charged ions regulate interior surface area, such polymers invented in Jena, but have been known the capacity of the lattice framework to could also be of use as catalyst for chem- in a variety of forms for some years. take up guest molecules and, as it were, ical reactions. The novel feature of JUMP-1, however, selectively open and close the »door« to

Original Publication A robust anionic pillared-layer frame- work with triphenylamine-based linkers: Contact ion exchange and counterion-dependent Prof. Dr Winfried Plass, Oluseun Akintola Phone: +49 36 41 9-48 130 sorption properties, CrystEngComm (2017), Institute for Inorganic and Analytical Chemistry Email: [email protected] DOI:10.1039/C7CE00369B Humboldtstr. 8, D-07743 Jena, Germany www.plass.uni-jena.de

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Excavating traces of ancient earthquakes

If there is an earth tremor anywhere in the world today, technical devices record even the tiniest movement. And if an earthquake causes serious damage, the media ensure that we know about it and that it is not so quickly forgotten. However, even catastrophes for which we have no records have left traces underground. Geoscientists are now uncovering this evidence.

BY SEBASTIAN HOLLSTEIN

Over the next three years, geoscientists per year,« says Grützner. This may be ty in this area. »At most, we can hope to from Jena will be working in a little- very slow when compared with other get information from the Romans, who known earthquake zone in Europe: earthquake zones, but it does not mean ruled the region around 2,000 years ago. Slovenia and eastern Italy. »Today, we that there is no seismic activity. Earth- There are no written records of any ear- are particularly aware of the major dis- quakes in May and September 1976 lier earthquakes,« explains Grützner, asters of recent years in the centre of the killed approximately 1,000 people and a geophysicist. »This means that there Italian Peninsula, but similar events can caused considerable damage in a num- could be geological time bombs ticking also occur in neighbouring areas,« ex- ber of towns. in this region, which nobody knows plains Dr Christoph Grützner. He leads about because they only explode every a project that is part of the priority pro- few thousand years.« gramme SPP 2017, funded by the Ger- Written records of historical quakes However, a close look at and under the man Research Foundation (DFG). Scien- are rare ground can help researchers to find tists from FSU Jena, RWTH Aachen and traces of past earthquakes. Grützner GFZ Potsdam are working together in There was a similar disaster in 1511, as explains: »First, I use the computer to this programme, doing research on the evidenced by historical documents. Due analyse high-resolution terrain mo- tectonic movements in this region. to the long gap between the individu- dels and look for particular structures al events, though, it is difficult to esti- in the landscape that indicate tectonic »The Adriatic Plate is continuously mov- mate average repetition rates at indivi- seam zones—for example, characteri- ing northwards towards the Eurasian dual faults, which could contain import- stic-looking river valleys. And then I go Plate, at a rate of about two millimetres ant information about the seismic activi- in person to look at the area.« At the site, he digs into the earth, ex- posing sedimentary layers in order to find striking deformation structures. Prof. Kamil Ustaszewski (l.) and Dr Layers that are normally arranged ho- Christoph Grützner study a map of the rizontally can be deformed. »This is Alps covering the area of Slovenia and how I identify faults from which earth- north-eastern Italy. quakes have been triggered in the past and could again be triggered in future. In addition, by dating the sedimentary layers I can draw up a possible chrono- logy of the seismic activity.«

Researching the origins of the Alps

However, this Adriatic region is in- teresting not only in relation to earth- quakes. The tectonic movements of the two plates are also responsible for the emergence of the Alps, says Prof. Kamil Ustaszewski. The professor of structural geology heads the working group of which Grützner’s work is also a part. »We are investigating how the Alps were formed and how the deep structures beneath them were created,« explains Ustaszewski. ProjectsRubrik 59

ARA Cluster of the Institute of Computer Science in the University’s Computer Centre. The High- Securing, using and sharing Performance Computer system (HPC) works with at least 300 processors. In order to obtain scientific information from the flood of digital data that is Constantly increasing amounts of scientific data from observations, currently available, high-performance computing experiments or measurements not only require greater computer storage and data-based sciences are working hand-in-hand. Sustainable research data management secures the capacity, but also sustainable research data management. This is current- treasure trove of data for the worldwide scientific ly being significantly expanded at Friedrich Schiller University in Jena. community and for future use.

BY UTE SCHÖNFELDER

Satellite images of climate data, re- To change this situation, the Universi- and that informs them about data ma- sults of sociological surveys, as well as ty Jena aims to deal with digital data nagement plans, data platforms or meta- growth curves of national economies or sustainably and efficiently, and to this data standards, for example. To this microorganisms—in nearly all scientific end it is expanding its research data end, existing services will be brought disciplines nowadays, new findings are management. In a project funded by the together and coordinated in the »Re- based on the analysis of large amounts Federal Ministry of Education and Re- search Data Management Helpdesk«, of digital data. Scientist frequently work search (BMBF), various building blocks set up in 2015. for years on accumulating these data- for effective and efficient research data »Additionally, we want to professional- sets, which then fill vast storage devices management will be developed and ise the processes for sustainable re- and require huge computing capacity tested by 2019. The project is receiving search data storage, and integrate them for processing. This constitutes a verita- around 467,000 euros in funding. into a national or international infra- ble »treasure trove« of data. »In many structure,« adds Roman Gerlach, who cases, such measurements are unique works with Prof. König-Ries in the »Re- and cannot easily be repeated,« no- International infrastructure search Data Management Helpdesk«. tes Prof. Birgitta König-Ries. From the With regard to the publication and long- point of view of science, it is absolutely »Our aim is to expand and improve our term storage of research data, Gerlach imperative to make efficient use of this range of services in the area of research refers to the existing »Digital Library of wealth of data. However, to date only a data management and of data collec- Thuringia«. Furthermore, project mem- small part of all primary data finds its tion, including secure data storage over bers will work with the international way into scientific publications, databa- the long term,« says Prof. König-Ries, scientific community to develop criteria ses or public archives, adds König-Ries, who leads the project. In practice, the and methods for sustainable quality as- who holds the Heinz-Nixdorf Chair for plan is to offer advice to researchers that surance in the area of research data ma- Distributed Information Systems. is specifically relevant to their discipline nagement.

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IS is using digital recruitment methods to further its radical aims.

and international research on radicali- sation over the next few years. »We will first be checking which developmental factors in adolescents correlate with extremist views and actions,« explains Beelmann. »We will then take a close look at the preventive measures that have been taken and investigate how effective they turned out to be.« The psychologists want to use the results of these analyses to develop new, effective preventive measures, which can then be implemented in a variety of practical contexts such as schools or within civic education and staff training. Beelmann began studying the topic of Preventing terrorism preventing violence in children and young people some years ago. »In the last 30 years, significant progress has Psychologists want to prevent young people from becoming radicalized— been made in this field,« he notes. In an increasingly complicated endeavour in the digital age. The Federal the case of the radicalisation of young Government is now providing three million euros to fund the development people, too, the task is now to let the of preventive measures. findings on radicalization processes flow into the development of preventi-

BY SEBASTIAN HOLLSTEIN ve measures. The psychologist also sees socio-political shortcomings, of which the scientists want to raise aware- ness: »For instance, young people with- Discussions about fighting terrorism »In principle, we assume that radicali- out qualifications or career prospects often centre on equipping the police sation processes work in very similar are a high-risk group; in radicalization or on military action. However, if one ways, regardless of whether right-wing they see opportunities for gaining the wants to find long-lasting methods for extremism or religious fanaticism is in- recognition that they are denied else- tackling politically or religiously mo- volved,« says Prof. Andreas Beelmann, where.« tivated offences, the key task is to pre- who leads the project at the University vent the perpetrators from becoming Jena. »However, because of the Inter- radicalized at a young age. Hence, over net, the situation has of course changed »Centre for Research on Right-Wing the next three years, psychologists at dramatically over recent years.« Where- Extremism, Civic Education and the University Jena will be develop- as in the past, like-minded people had Social Integration« ing measures to prevent the radica- to make much more effort to make con- lisation of young people as part of a tact with each other, this has become The project also adds a priority rese- project funded by the Federal Minis- much easier in the digital age, as well as arch area to the work of the Centre for try of Education and Research. In the much harder to monitor. However, this Research on Right-Wing Extremism project »Radikalisierung im digitalen does not have to mean that young peo- at the University of Jena. In addition, Zeitalter« (Radicalisation in the Digital ple are more likely to become radicali- the Free State of Thuringia has extend- Age)—RadigZ for short—they will be sed. »It is still a minority of members ed and significantly boosted its fund- working with seven other institutions of a cohort or generation who go on to ing of the Centre, which, as a result of in Germany, organised by the Crimi- express a radical ideology in criminal its new tasks and objectives, now bears nological Research Centre of Lower actions,« says Beelmann. Together with the name »Centre for Research on Saxony. The Ministry is providing the psychologists, Dr Sara Jahnke and Right-Wing Extremism, Civic Educa- three million euros for the project, of Clara Neudecker, he will be systemati- tion and Social Integration«. which 350,000 euros go to Jena. cally collecting and analysing national ProjectsRubrik 61

Prof. Andrey Turchanin investigates nanoscale 2D materials such as graphene.

The best of two nanoworlds

An international team of scientists coordinated by Jena professor of physical chemistry Andrey Turchanin is working on new applications in the area of flexible electronics by developing ultrathin hybrid sheets of organic semiconductors and inorganic atomically thin 2D materials. The research project is supported with 847,000 euros by the EU funding programme FLAG-ERA.

BY JULIANE DÖLITZSCH

It is every researcher’s dream: an inven- on their invention of an ultrathin sheet ough characterization of the properties tion is followed by a patent application, made of organic semiconductor pen- through microscopy and spectroscopy. a renowned scientific journal then pub- tacene. Previously, the results of their Using the layer-by-layer assembly of or- lishes the research results, and, finally, a research were published in »Advanced ganic and inorganic nanosheets, the hy- funding agency provides nearly a mil- Materials«. In collaboration with scien- brids with the desired properties will be lion euros in order to make the idea a tists from the Netherlands and Sweden, produced: »flexible, conductive, switch- reality. It is precisely what has come true the researchers are further developing able, and environmentally friendly,« for Prof. Andrey Turchanin of the Insti- this novel nanomaterial with a thickness explains Turchanin. Among potential tute of Physical Chemistry. of only 50 nanometres. applications of these materials, he sees In October 2017, the EU programme flexible electronic devices including dis- FLAG-ERA announced which proposals plays, solar cells and sensors. will be supported within the Flagship Assembly with atomically thin sheets Since the discovery of insulated single- projects Graphene and Human Brain layer graphene sheets, research of gra- over the coming years. The only pro- »We will use the funding to create new phene and related 2D materials has ject to be selected that is coordinated applications for organic semiconductor been one of the hottest topics in physics, from Germany was »H2O«—Hetero- nanosheets, for which we have applied chemistry and materials science. This structures of 2D materials and organic, for a patent, by combining them with field is considered to be so promising semiconducting nanolayers—which inorganic atomically thin 2D materials that since 2013 the European Union has was funded with 847,000 euros for three such as graphene and transition metal dedicated one its two major research in- years from January 2018. In this initia- dichalcogenides, thus employing the itiatives to developing and implement- tive, project leader Prof. Turchanin and best properties of these two complemen- ing these nanomaterials. Annual calls Dr Bert Nickel from Ludwig Maximi- tary material classes,« explains Turcha- for proposals such as FLAG-ERA aim to lian University in Munich are building nin. The project will start with a thor- attract innovative ideas to this initiative.

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spectrum of disciplines such as geology, Haussknecht’s oriental souvenirs geography, cartography, zoology, local customs, and social and cultural histo- ry, is of importance in interpreting the Botanists in Jena and partners are launching a project to publish the ori- botanical material,« says project director ental travel diaries of Thuringian naturalist Carl Haussknecht. The cultural Hellwig. »The diaries are thus cultural history project has been awarded some 400,000 euros in funding. and historical documents.« Important for this cultural dimension is also the

BY AXEL BURCHARDT fact that Haussknecht never intended for the diaries to be published, with the result that they contain very personal Travellers return home enriched by new large interdisciplinary project involv- thoughts and impressions of people and experiences and often with a few souve- ing several universities. The German of the political situation. nirs in their luggage. Carl Hauss­knecht Research Foundation (Deutsche For- Project collaborator Kristin Victor and (1838-1903), too, brought back »souve- schungsgemeinschaft DFG) is funding her colleagues face the challenge of nirs«—thousands of them—from his the three-year project, which also in- deciphering and »translating« Hauss­ journeys through the Ottoman Empire volves the universities of Halle-Witten- knecht’s antiquated cursive writing. and Persia, which he started in 1865 berg and Marburg, with 400,000 euros. Future tasks also include identifying and 1866. There, the naturalist found and annotating plant names, geographi- and collected plants, which represent cal designations, local conditions and a significant part of the herbarium that Haussknecht’s personal thoughts on events, as well as evaluating their scien- Haussknecht created. Raised as a foun- people and politics tific, cultural and historical relevance. dation in 1896 in Weimar, the herbari- um has long been in the possession of »On the one hand, we want to find out In order to make the annotated writ- the University Jena. But besides plants, more about our collection,« says botanist ings accessible worldwide, the team is Haussknecht brought back 15 octavos Prof. Frank H. Hellwig. This is because receiving support from the Thuringian closely written in Kurrent, an old form the exact size of the collection is not yet University and State Library. Finally, of German handwriting, totalling 1,000 known. On the other hand, the diaries science historian Dr Andreas Christoph pages describing his travels and the help to investigate and deduce the des- is responsible for designing the digital plants (photo top). These travel dia- ignations of certain plants. »What we presentation of the research results. The ries, which are kept at the Institute of have seen so far shows that the infor- project’s comprehensive Internet pre- Ecology and Evolution, will now be mation in the diaries, which extends sence is planned to go online before the digitally published and annotated in a beyond pure botany to take in a broad end of the project in 2020. TickerRubrik 63

His and hers medicine cabinets

Testosterone makes anti-inflammatory drugs work differently in women and men

Susceptibility to particular diseases is different in men and women, with inflammatory diseases such as asthma, pso- riasis or rheumatoid arthritis being much more common among women than men. Pharmacists working with Prof. Costly decisions Oliver Werz, together with colleagues from Italy, Denmark and Sweden, have uncovered a significant cause for these sex differences at the molecular level. In two high-profile publica- Economist uncovers irrational management tions in the »Journal of Clinical Investigation« and »Scientific decisions for product innovations Reports«, they show how the male sex hormone testosterone interferes with the biosynthesis of inflammatory substances, and additionally reduces the effectiveness of anti-inflammat- Disadvantage is a fact of life: women have a hard time in ory drugs (DOI: 10.1172/JCI92885; DOI: 10.1038/s41598-017- areas traditionally dominated by men; foreigners often 03696-8). have to struggle against prejudice; and in Germany, peo- To this end, the researchers comprehensively analysed and ple from the former East Germany are less likely to be in compared inflammatory processes in diverse animal models, senior positions. These are facts that have been scientifical- but also in immune cells from the blood of male and female ly studied and substantiated. Economic researcher Ronny human donors. »We investigated the formation of inflammat- Reinhardt (photo above) has now discovered yet another ory substances, such as leukotrienes and prostaglandins, and group facing discrimination: cheap new products. It ap- looked at whether the effect of anti-inflammatory drugs dif- pears that managers and decision-makers in companies fers in male and female cells,« explains Werz. avoid these and show a preference for expensive product innovations. This is demonstrated by Reinhardt and his co-authors from Switzerland and the USA in their essay »The High-end Bias—Investigating the Irrational Prefe- rence for High-end over Low-end Innovations«. In their recent study, the researchers found out that in innovation projects, managers opt for products from the more expensive end of the range in around 80 per cent of cases. »With the same investment and the same return for the company, decision-makers are more likely to choose to bring expensive products to market.« They give preference to the higher-class products and would rather have fewer customers with more money than a lot of customers with little money. »They tend to reject low-cost innovations,« explains Reinhardt. The study gives clues to possible reasons for this: expensi-

Do we need separate »his and hers« drugs? Pharmacists show that inflammations ve products have positive connotations, reflect high value need to be treated differently in men and women. and a certain status—factors that are clearly important to managers at manufacturing companies. »These feelings influence investment decisions, although As expected, the effect of the drugs under investigation was they are not appropriate. This ultimately means fewer new significantly stronger in the female samples than in the male products for those with limited budgets,« adds Reinhardt. samples—after all, the inflammatory process is much more pro- The economists collected their data by means of experi- nounced in women. However, these differences are completely mental surveys and two reaction tests in which associa- abolished by the administration of testosterone. Previous stu- tions were recorded that were made by over 500 partici- dies—including work by Prof. Werz’s team in Jena—have alrea- pants from small and large companies in a wide variety dy shown that testosterone can protect against inflammatory of sectors. A study of a dataset relating to more than 2,000 reactions. »However, now we have been able to throw light on product launches in the USA additionally shows that in the molecular mode of action and show that testosterone also supermarkets, the result was high product diversity in the influences the therapeutic effect of drugs,« notes Werz. With high price range and little choice in new low-cost food pro- this work, the researchers have once again provided concrete ducts—even though from 2010 to 2011 cheaper products evidence supporting the need for gender-specific medicine. US accounted for twice the turnover of expensive ones. jd

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How fish made What makes the move to land mushrooms »magic«?

The garfish’s cucullaris muscle give insight into the »Magic mushrooms« evolution of terrestrial vertebrates have their strong psyche- delic effect due to a sub- The garfish has been swimming in the waters of our planet stance called psilocybin, for more than 140 million years, yet it still holds secrets. which has been known Evolutionary biologists from Jena have unravelled one of for nearly 60 years. One these secrets gaining important information about how mystery remains, how- fish developed into terrestrial vertebrates. Benjamin Nau- ever: how exactly do mann (photo below) and Prof. Lennart Olsson from the In- mushrooms of the genus stitute of Evolutionary Biology have succeeded for the first Psilocybe (on the photo) form this active substance? A team led time in correctly identifying the »cucullaris« muscle in this by Jena-based natural substance and fungi expert Prof. Dirk fish species. This muscle shows many similarities with the Hoffmeister has now solved this mystery. The researchers suc- cucullaris muscle of terrestrial vertebrates. The scientists ceeded in identifying the enzymes that help the mushrooms reported on their research results in the specialist journal to form their magic substances. In addition, through their re- »Evolution & Development« (DOI: 10.1111/ede.12239). search they established that the biosynthesis occurs in a diffe- rent order from that described in earlier studies. Their results »We have corrected an error made over a century ago, appear in the journal »Zeitschrift Angewandte Chemie« (DOI: because in earlier investigations a different muscle was 10.1002/anie.201705489). classified as the cucullaris muscle in the garfish,« says Using the model bacterium Escherichia coli, it was possible to Benjamin Naumann. The evolutionary biologists are inter- produce the previously identified enzymes. In this way, Hoff- ested in the muscle which connects the head to the shoul- meister and his colleagues were able to reproduce the synthe- der girdle in particular because it is present both in ancient sis of the active substance and produce psilocybin without fish and in mammals, although its function has changed fungal cells. In future, this very effective molecule could be substantially during evolution. »In fish, the head rests di- produced more easily in this fashion, as apart from its use rectly on the shoulder girdle, which means that the head as a recreational drug, this substance also has useful healing cannot move independently from the body,« explains Prof. properties. In small doses, for example, it can reduce anxiety Olsson. This direct connection has been done away with in in patients with life-threatening cancers or relieve the symp- terrestrial vertebrates. They developed a neck which enab- toms of depression and lethargy. MR led them to move the head independently from the torso. This new study in Jena has made it clear that in the garfish, too, this muscle is present between the body and the head. Previously, researchers had erroneously assumed that a different muscle near the gills was the cucullaris. »The po- How mammalian teeth get their shape sition of the cucullaris muscle is important because it re- veals to us that it is formed exactly as it is in mammals, for example,« says Naumann. »Developmental biology there- The teeth of hairless dogs are giving scientists clues to the de- fore shows us a homology in this case indicating that the velopment and evolution of teeth in mammals. Hairless dogs muscle has a common evolutionary origin in both animal differ from other dogs not only due to their lack of fur, but also groups.« sh in the number and nature of their teeth. Researchers from the Max Planck Institute for Evolutionary Anthropology in Leip- zig and Friedrich Schiller University Jena have re-examined almost 100-year-old skulls and teeth of hairless dogs from the collection of Jena’s Phyletic Museum, and they have estab- lished that a gene called »FOXI3« is involved in the develop- ment of teeth. They presented their results in the journal »Scientific Reports« (DOI: 10.1038/s41598-017-05764-5). The team, led by associate professor Kornelius Kupczik and Prof. Martin S. Fischer, was able to show that in the hairless dogs, nearly all the permanent teeth that replace milk teeth (i.e. incisors, canines and premolars) were missing, while the molars were present. It was also noticeable that on these teeth, certain dental cusps on the side nearest the tongue had not developed. The researchers assume that »FOXI3« also plays a role in the development of teeth in other mammals, including humans. US TickerRubrik 65

Crossing borders

Four-volume encyclopaedia provides first comprehen- sive overview of private international law

In the 21st century, many people’s lives are very internatio- butions on private law topics. Volume three encompasses nal. They travel all over the world, buy goods from countless country reports on private international law from 80 states, countries and marry people from other cultures. But what including Thailand, Tunisia and Nigeria, which had hardly happens if the flight is cancelled, the car breaks down or a been described before. Finally, the fourth volume contains couple falls out of love? »Law has not managed to keep pace a collection of legal texts from all over the world, translated with the dramatic internationalisation of our lives. It is still to into English. »This volume is of central importance for further a great extent national and looks different in Germany from research, because it makes many laws available to an inter- the way it looks in England, France or Italy,« says Prof. Giesela national readership for the first time,« says Prof. Rühl. The Rühl (photo on the right). Her area of expertise, private inter- entire work will soon be found on library shelves, mainly of national law, is concerned with the question of how to solve universities and other educational institutions. jd the problems of cross-border legal relationships. Rühl explains that with globalization the number of international disputes and legal proceedings has in- creased. National and international lawmakers, but espe- cially the European Union, have responded to this situa- tion in recent decades and have adopted appropriate re- gulations. However, an overview of this confusing and rapidly growing area of law has been lacking—until now. The »Encyclopedia of Private International Law«, coordi- nated by Prof. Rühl’s department, has just been published. The four-volume English-language work contains 4,000 pa- ges that comprehensively describe the history, methods and content of private international law. As the central coordina- tion point, Giesela Rühl’s department brought together all the threads of the mammoth project funded by the Fritz Thyssen Foundation, which involved 181 authors from 57 countries. The first two volumes of the encyclopaedia contain contri-

Laser beams from the sky How does hypnosis work?

Laser beams are frequently used to study the chemical com- Psychologists at the Department of Biological and Clinical position of the atmosphere. Researchers send laser pulses into Psychology have shown that even an imagined »obstruction« the sky and then analyse the light that is scattered back. How- can disrupt a person’s vision. In the journal »Scientific Re- ever, it would be better if the light could also return to earth ports« they presented the results of a study that reveals what as a laser beam, because its light sends a stronger signal and happens in the brain of a person under hypnosis when proces- it is easier to read information from it. Dr Daniil Kartashov of sing visual stimuli (DOI:10.1038/s41598-017-05195-2). the Institute of Optics and Quantum Electronics in Jena and For her experiment, Dr Barbara Schmidt of the working group Prof. M. Shneider of Princeton University (USA) have now es- led by Prof. Wolfgang Miltner tested three groups of partici- tablished the theoretical principles for such sky lasers (DOI: pants: people who were very suggestible and easy to hypno- 10.1063/1.4978745). tize; people who were moderately suggestible; and a group of For this, the researchers exploit the properties of the air. The people who were more resistant to hypnosis. Under hypnosis, use of ultrashort laser pulses creates a kind of »lens« in the air. participants had to count symbols on a screen in front of them. This lens focuses more strongly the laser beam that is emitted At the same time, they were told to imagine that there was and creates fine plasma channels. The light in these filaments, a wooden board in front of their eyes. The suggested visual as they are called, supports a broad spectrum of radiation, blockade made the number of counting errors rise sharply. which can provide information on the chemical composition The participants’ brain activity, which was recorded via EEG of the environment. By selecting suitable parameters, such as during the task, showed that their basic visual perception was plasma temperature and density, the laser can interact with intact, even with the imagined obstruction. However, sec- the nitrogen in the atmosphere in such a way that a real sky ondary processing operations, such as counting the symbols, laser is produced. sh were impaired. sh

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More safety—more risk?

Does wearing a safety gear like a bike helmet affect a person’s willingness to take risks? Psychologists at the Department of Biological and Clinical Psychology are investigating this question. The photograph shows stu- dent Jona Ebker (l.) monitoring such a psychological experiment. The test person in this case is Dr Barbara Schmidt (r.), who is leading the study. She has to com- plete a series of tasks including risk decisions with and without a helmet, while her brain activity is recorded via the electroencephalogram (EEG). Science Photo 67

03 | LICHTGEDANKEN 68 RubrikPortrait

The art of science and science of art

Unlike most medical students, Prof. Christoph Redies never wanted to practise medicine. Instead, from early on in his research career, he wanted to pursue, in a scientific way, his second great passion: art. Christoph Redies with one of his abstract works from 2001.

BY JULIANE DÖLITZSCH

During last year’s Jena University Summer Party, anyone ted in the natural sciences.« He did not necessarily wish to who took a look at the small art exhibition in the canteen on become a doctor, but wanted to keep other options open. Philosophenweg was bound to be attracted by the abstract compositions framed in heavy, valuable wood. Their crea- After the first years of medical studies in Essen, he consi- tor, Prof. Christoph Redies of Jena University Hospital, was dered studying the biological foundations of art. However, always to be seen nearby. The professor of Anatomy was in the 1980s the time was not yet ripe for such research. Re- very happy to answer the call for University staff to exhibit dies specialized in vision research and the molecular basis their photographs and paintings in the Summer Party’s art- of brain development. The last year of his medical studies ists’ studio. Redies not only showed watercolours, oil paint- resembled a clinical world tour, taking him to Adelaide ings, pastels and etchings, but also set up a video installa- in Australia, Boston in the USA and Montreal in Canada. tion and displayed a collection of his scientific publications. However, practical work in hospitals failed to stimulate his The topic was Experimental Aesthetics. With great enthusi- interest in working as a doctor. »After obtaining my licence asm, he explained his research to a large number of visitors. to practise medicine, I hung up my white coat and never saw patients again,« notes Redies. And so, after finishing »I would like to find out what constitutes the structure of his medical dissertation at the Max Planck Institute in Göt- a beautiful piece of art,« explains Christoph Redies. »What tingen, he wrote a doctoral thesis in neurosciences in Mon- does a picture have to be like in order to be considered aes- treal, thus obtaining a PhD. After postdocs at the Massa- thetically pleasing?« This question has always preoccupied chusetts Institute of Technology (MIT) in Cambridge and the 59-year-old professor, just as art has always been an in- Japan’s Kyoto University, he returned to Germany. In 1997 tegral part of his life. The son of international art dealers, he was appointed Professor of Anatomy at the University who ran a gallery for modern art in Düsseldorf, Redies be- of Essen and in 2003 at the FSU. He attributes his success­ gan painting at the age of 16. The self-taught artist spent the ful academic career to his research in molecular biology summer of 1977 in a studio in Paris, but subsequently decid- and brain research, as his other research ideas relating to ed to study medicine in Essen. »I was not ready to cope aesthetics were initially seen as fanciful. with the uncertainties of an artist’s existence,« he recalls. However, he does not want to describe his academic choice However, Christoph Redies’s research interests became as simply being a rational one: »I have always been interes- acceptable at last when the state of Thuringia competed— Rubrik 69

Christoph Redies created the etching »Paris« in 1977 during his stay in the French capital.

unsuccessfully—to become the site of the new Max Planck many things he wants to accomplish in science before this Institute for Empirical Aesthetics. »At the start of my ca- father of four daughters retires. He would like to get even reer, I would have ruined my academic reputation if I had closer to the heart of what constitutes beauty in an artwork. pursued my research interest in art, but technology has sin- In addition, in his research he would like to turn his atten- ce undergone huge developments. In addition, as early as tion to music. In his youth, Redies played the piano for nine 2005 I found an open-minded collaborator in Prof. Joachim years, »but not particularly well,« he says with a laugh. But Denzler,« says Redies. Together, the physician and the IT his penchant for classical music has stayed with him. specialist laid some of the foundations for research on the Research is first and foremost an intellectual game for him, aesthetics of art. His research group currently works with a and he experiences joy in being curious and in making team from the Institute of Psychology. He does not see him- discoveries. Art, on the other hand, can connect people and self as a trendsetter, but readily admits that »it’s exciting to cultures, and can move people more deeply. For a long time, be part of a new, developing field of research right from its it was his dream to combine the two, and he has now been beginnings«. Aesthetics has now actually become a trendy able to fulfil his dream for the last 12 years at the Institute academic topic. As evidence for this trend, several research of Anatomy, of which he is the Director. In this position he associations have thrived in this field, such as the Interna- benefits not only from being located in Jena: »As a professor tional Association of Empirical Aesthetics, of which Redies at a German university, you have the freedom to investigate is of course a member. whatever you like—and that’s fantastic.«

And what is the structure of a beautiful artwork all about? Structure of beauty in the visual arts and music »The way in which an artist paints often imitates the struc- ture of complex natural scenes,« explains Redies. As a re- Does Redies paint differently since he has started studying sult, because our visual system is adapted to process natural the subject so intensively? »Thinking is not necessarily structure and patterns, humans find artworks familiar and helpful when one is painting,« he replies, »but rather it is perceive them as beautiful—and the richer and more varied feeling that counts. And my feelings have not changed.« In they are, the more beautiful they seem. »It’s difficult to ex- any case, he does not have much time for painting at the press this in simple words,« notes Professor Redies. It would moment—science is still the top priority, because there are be easier using brushstrokes.

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»GEO« sends student on research trip

Mauro Alivernini, a doctoral candidate in the Group of General and Historical Geology, has travelled to Ghana in West Africa to test a new environmental monitoring method. The 31-year-old Italian is investigating whether ostracods and foraminifera—tiny aquatic creatures—can be used as bioindicators for the ecological state of coastal waters. The trip was made possible by a grant from the educational magazine »GEO«. This means that the results of Alivernini’s research will be found there as well as in specialist journals.

BY UTE SCHÖNFELDER SCHWERPUNKT 71

Photo left: Natural paradise on the west coast of Ghana. Photo right: Geoscientist Mauro Alivernini, accompanied by a Ghanaian fisherman, sails through a mangrove forest close to shore, near the Amanzule River.

It is early September and in Thuringia in the open air, without any protection Back in their own laboratory, Aliver- the weather is mild. Mauro Alivernini for the soil, water or the workers them- nini and his colleagues are studying stands with a colleague in a pedalo in selves. Rainwater washes away heavy ostracods and foraminifera: microscopi- the middle of the artificial lake at Ho- metals and other harmful substances, cally small creatures that live in bodies henfelden, some 20 kilometres south of which find their way into the lagoons of water around the world. Just a few the Thuringian capital Erfurt. The boat on the city’s edge, and from there they millimetres in size, »they are normal- wobbles as, helped by Thomas Biehl, the are carried out to sea. »These are ex- ly completely uninteresting for people. athletic young man pulls a two-metre- treme examples of environmental da- After all, they don’t transmit any di- long plastic cylinder, with metal mage, which is being caused here and seases and you can’t eat them«, jokes weights attached, out of the water and is spreading at an alarming rate,« says Alivernini. However, the tiny creatures into the boat. Water, brown from the Mauro Alivernini. Ecological standards are of enormous value for him and for churned-up mud, runs down the sides are virtually non-existent and few other geologists: they accumulate in se- of the cylinder, soaking Alivernini’s people in Ghana are environmentally diments and provide information about feet. He looks satisfied: the sediment aware. The environmental destruction the state of the water in which they live. sample from the lake bottom promises is particularly severe along the coast, to provide sufficient research material. where the bulk of the population lives. Foraminifera are single-cell organisms— The sampling session was a success. amoeba—which are usually enclosed in a calcareous shell. They occur prin- Four days later, Alivernini, Master’s Sustainable coastal management cipally in the sea. Ostracods are equally student Thomas Biehl and Ghanaian tiny crustaceans that live in all types of scientist Lailah Akita are on a plane to With their research, the scientists want bodies of water. »These organisms react Ghana. Their destination is Accra: the to create the conditions for sustain- very sensitively to changing environ- country’s capital and economic hub, able coastal management in Ghana, mental conditions,« explains Aliverni- and one of the most polluted places and to this end they have been doing ni. Temperature fluctuations, changes on Earth. On board are the scientists’ ground-breaking work. Over a three- in the salt content of the water or in- sampling and measuring devices. Ali- week period from 9 to 27 September, fluxes of contaminants quickly lead to vernini and his colleagues want to test a they took sediment samples from vari- morphological alterations to the creatu- new environmental monitoring method ous bodies of water, first in Accra and res’ tiny calcareous shells. For this rea- in the West-African country. Ghana is a its heavily contaminated surroundings, son, the creatures’ appearance and the dumping ground for Europe’s electro- followed by the lagoons and mangro- species composition enable researchers nic waste. On huge rubbish dumps in ve forests in the less polluted western to assess environmental conditions Accra, computers, photocopiers, fax ma- coastal area of the country. They ana- such as water quality, and even to draw chines and television sets from the west- lysed the first samples in Ghana, and conclusions regarding climate change ern world are disposed of. Workers ex- also brought around 10 kilos of sieved over the long term. »In some countries, tract valuable metals from the devices and dried sediment back to Jena, in or- ostracods and foraminifera are already simply by burning the plastic housing der to examine it in detail. used routinely for environmental mo-

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Local people help the researchers from Jena to load the inflatable boat and equipment near Keta Lagoon in the east of the country.

nitoring, for example in Norway,« says Alivernini. The researchers now want to make this possible in Ghana as well, because the method is simple, but very effective and—what is more—cheap.

Inventory of the microfauna

All one needs is an average optical microscope and knowledge of the typi- cal composition of the local microfauna. The researchers used their expedition to Ghana to prepare a precise invento- ry of the ostracod and foraminifera fauna in the coastal waters. Some of the sedi- Beach strewn with rubbish near the Ghanaian capital Accra. The ground is sealed by a thick layer of oil, which prevents rainwater from seeping away. Here too, Mauro ment samples are currently being ana- Alivernini took sediment samples: within just a few minutes, the researcher sank lysed by scientists from the University up to his thighs in the mud. It was only with a great effort that he managed to free of Accra. Other samples are being ana- himself from the soft soil, which offers no support. Locals report that every year, a lysed by Alivernini and his colleagues number of people simply disappear into this morass. in Jena, under the direction of micropa- laeontologist Peter Frenzel. Initial results from the heavily polluted region around Accra show a multitude of deformations in foraminifera shells. »We’ve never seen anything like it befo- re,« remarks Alivernini. The aim is now BACKGROUND to document the spread and ecology of the bioindicators for the Ghanaian coastal region, and assess the current With his research project on ostracods and foraminifera as bioindicators, Mauro Alivernini won environmental situation. »Over the »GEO«’s 2016 expedition grant. The 31-year-old geologist was chosen from among more than 50 long term we want to develop a moni- competitors from all over Germany. Alivernini used the 10,000 euros for a trip to Ghana, during toring programme for the West African which he and two colleagues took extensive sediment samples for the current analyses. Two jour- coast, based on ostracods and foramini- nalists from »GEO« magazine accompanied the Italian scientist for several days during his field fera,« says Alivernini of the group’s fu- work in Africa. The magazine will report on the young researcher’s work in one of its next issues. ture plans. SCHWERPUNKT 73

»GEO« photojournalist Dominic Nahr (centre) watches Thomas Biehl (left) and Mauro Alivernini preparing samples in their open-air laboratory at the University of Accra. The photographer and two journalists from the educational feature magazine accompanied the Jena scientists during their work for a whole week.

The sediment samples from the different coastal regions are washed, sieved and then dried, before they are put under the microscope. The researchers brought at least 10 kilos of dried material back to Jena, in order to analyse it further.

Foraminifera from sediment samples that Alivernini and his colleagues collected in the heavily contami- nated region around Accra. The shells of the single- cell marine organisms are severely deformed. Above left is a normally shaped specimen of the genus Quinqueloculina.

03 | LICHTGEDANKEN 74 RubrikBehind the Scenes

Research in Microgravity

The materials scientist, Prof. Markus Rettenmayr (Photo above), experienced a microgravity parabolic flight last summer. He talks here about the fascina- tion of weightlessness and suffering in the cause of science. Doctoral candidate Robert Hanke (seen here during a flight in 2016) remained earth-

BY STEPHAN LAUDIEN bound in Bordeaux on this occasion and provided the team with technical support.

If you have a burning desire to float in zero gravity, there is no lic flights is the German Airbus A 310 that used to carry the need to fly to the ISS, as you can experience this phenomenon German Chancellor. Where Angela Merkel and her entourage on a parabolic flight. The European Space Agency (ESA) offers used to sit, there is now equipment to be used in a variety of such flights in partnership with the German Aerospace Cen- experiments. There is also a system of belts and straps, so that ter (DLR), with a special airplane taking off from Bordeaux in weightless passengers do not completely lose control. Only in France. Flights are carried out for the purposes of scientific the rear of the plane are there still seats. research, but also for simple curiosity, as in some cases tourists can also book a flight. »Weightlessness starts very suddenly—there’s no transition »It’s like being seasick, but worse!« phase,« says Prof. Markus Rettenmayr. You have to be careful, as spontaneous movements can quickly lead to violent colli- Before the flight, passengers take medication against mo- sions, adds the scientist from the Otto Schott Institute of Ma- tion sickness. »It feels as if you’re seasick, but worse,« says terial Research. If you are squatting on the floor of the aircraft Rettenmayr. Headaches, nausea and vomiting are common when weightlessness starts and try to stand up in the usual symptoms, which is why parabolic flight aircraft have been way, you will bash your head against the ceiling. Not for noth- nicknamed »vomit comets«. After taking off from Bordeaux, ing are there four helpers and a doctor on board, and the ceil- you first fly out over the open sea and a quiet area is sought ing of the plane is also padded. for the parabolic flights. The Airbus pilots then accelerate to Rettenmayr took his first parabolic flight last summer, and it 2 g—twice the acceleration of gravity—and pull the nose of was probably also his last. Not because he did not enjoy it, but the plane up to an angle of 50 degrees. After the climb, the rather because other scientists working on the same research engines are throttled and the plane follows the path of a tra- project would also like to have a go at zero gravity. During jectory parabola, during which passengers experience 22 sec- the flights, Rettenmayr and his team investigate how melted onds near absolute weightlessness. The plane then returns to metal alloys resolidify in crystalline or vitreous form. The aim the horizontal. The changes in gravity imply flying close to is to eliminate the influence of gravity as much as possible in the aircraft’s technical limits, says Rettenmayr, adding: »This this process. Highly sensitive measuring devices are used, flying manoeuvre demands great skill.« It is no wonder that which measure factors such as viscosity, thermal conductivity the crew consists of four former military pilots. One flight day and solidification velocity. »These experiments will be extend- involves around 30 parabolas, with a one-minute break after ed later on aboard the ISS,« says academic employee Robert each period of weightlessness. Hanke. The parabolic flights are a necessary preparation for The passengers enjoy floating around inside the aircraft. The the experiments on the space station. The long-term goal is to physical discomfort of motion sickness is the price that must obtain a model for the solidification behaviour of metal alloys be paid. However: »One or two days later, everything is fine that is as precise as possible. The plane used for the parabo- again!«