German Research Foundation extends project aimed at combating multi-resistant Acinetobacter baumannii strains
FRANKFURT. Cases of multi-resistant bacteria in hospitals have increased dramatically in recent years and the health system faces tremendous problems as a result. Alongside “old acquaintances”, such as Staphylococcus aureus (MRSA) or Klebsiella pneumonia, another pathogen has now arrived on the scene: Acinetobacter baumannii. In order to find new weapons for the fight against this aggressive germ, in 2014 the German Research Foundation established a Research Unit led by Goethe University Frankfurt which has now been extended for a further three years.
Infections with Acinetobacter baumannii are often fatal due to this bacterium’s increasing antibiotic resistance. In some European countries, over 90 percent of isolates no longer respond to antibiotic therapy. Particularly worrying is the fact that the pathogen is continuing its rapid advance throughout the whole world.
In order to obtain results in this situation that can be put to use as quickly as possible in clinical practice, natural scientists and physicians are working closely together in the Research Unit “Adaptation and Persistence of Acinetobacter baumannii”. Several institutes at Goethe University Frankfurt – Molecular Microbiology & Bioenergetics, Medical Microbiology & Infection Control, the Institute of Cell Biology & Neuroscience and the Institute of Biochemistry – are involved in the project together with the Robert Koch Institute and the universities in Cologne and Regensburg.
“We have achieved something quite unique: We use patient isolates, sequence their genome and analyse their pathogenic properties, which are then characterized with regard to countermeasures,” explain Professor Volker Müller, microbiologist, and Professor Volkhard Kempf, microbiologist and physician, who are the Research Unit’s two spokespersons. It has already been possible to identify first virulence traits by means of this approach.
The researchers know meanwhile what the bacterium feeds on, how it survives stress, how it adheres to animate and inanimate surfaces and how it withstands antibiotics. This knowledge enables them to test new targets for deactivating the bacterium. They discovered, for example, that bacteria are no longer able to trigger infections if you take away their ability to synthesise a certain sugar (trehalose). The research team is now working hard to shed light on this sugar’s biosynthesis process so that inhibitors can be developed.
The evaluators found this work so convincing that the German Research Foundation has not only extended the project but also increased its budget. The work undertaken in future will produce new answers to the question of how this increasingly threatening bacterium can be treated.
A picture can be downloaded from: www.uni-frankfurt.de/70620941
Caption: Petri dish with colonies of the dangerous hospital pathogen Acinetobacter baumannii.
Photo: Goethe University Frankfurt
Further information: Professor Volker Müller, spokesperson of Research Unit 2251, Molecular Microbiology & Bioenergetics, Faculty of Biological Sciences, Riedberg Campus, Tel.: +49(0)69-798-29507; email@example.com.
Professor Volkhard Kempf, University Hospital Frankfurt, Institute for Medical Microbiology and Infection Control, Faculty of Medicine, Niederrad Campus, Tel.: +49(0)69- 6301-5019, firstname.lastname@example.org, http://www.bio.unifrankfurt.de/51172482
ERC Starting Grant for research into predictive memory systems across the lifespan
FRANKFURT. Goethe University Frankfurt can boast another EU-funded research project: With the appointment of Yee Lee Shing as Chair of Developmental Psychology her PIVOTAL research project has accompanied her to Frankfurt. Professor Shing’s research work investigates how the brain makes predictions.
Imagine coming into the office in the morning. Within a split second you will be able to tell whether everything is in its usual place – the furniture, the computer, your files – or not, as the case may be, or whether something has been left on your desk that does not belong there, for example a box of chocolates. Behind this ability to assess our environment is the “predictive brain”, i.e. the interaction of brain processes that lead to predictions. On what principles these predictions are based and how the interaction of the processes involved differ across the lifespan is the subject of research work being conducted by Professor Yee Lee Shing, who has held the Chair of Developmental Psychology at Goethe University Frankfurt since January.
According to Professor Shing, the brain is essentially a “prediction machine” that is constantly busy comparing new input from the environment with predictions generated by internal models of the brain. Only in this way is the human brain able to adapt to ever new situations and grasp new environments. To date, however, no researcher has examined the nature of the underlying internal models themselves or how new experiences influence these models. What is also so far unknown is how such a supposedly universal principle manifests itself in different brains – for example young or old ones. The long-term memory that may underlie the brain’s internal models is potentially the episodic and the semantic memory, personal experiences on the one hand and learned knowledge of the world on the other. Whilst children are better at remembering episodic contexts – think how unbeatable they are when playing “Memory” – older people can rely more on their semantic memory.
Shing wants to investigate empirically the interaction of different types of memory and new experiences. Using the magnetic resonance facilities available at the Brain Imaging Center of Goethe University Frankfurt, she wants to learn more about which cognitive and neural interactions take place where in the brain, first of all with the help of healthy participants of different ages. In the long term, her research work could help to cast light on clinical conditions with aberrant prediction processing, such as autism and schizophrenia. The European Research Council (ERC) will support the project for five years with € 1.5 million. This will fund two doctoral and two postdoctoral researcher positions.
Born in 1980 in Kuala Lumpur (Malaysia), Yee Lee Shing moved to the USA at the age of 19 to study psychology. From 2004 to 2015 she worked at the Max Planck Institute for Human Development in Berlin. She also held a Humboldt Fellowship there at Humboldt University.
“I found the broad perspective on the development of the human brain across the lifespan very interesting. In addition, the new International Max Planck Research School on the Life Course (LIFE) offered me an interdisciplinary and trans-Atlantic research context,” she says, explaining her decision at that time to come to Germany. Shing’s doctoral supervisors were Professor Ulman Lindenberger and Professor Shu-Chen Li. Shing was a lecturer at the University of Stirling in Scotland from 2015 onwards.
Professor Shing was still working in Stirling when she submitted her project proposal. Her decision to return to Germany and accept the appointment in Frankfurt is also partly due to Brexit: “My husband and my two children are German. We felt that our future in Great Britain was uncertain. After so many years in Europe I didn’t want to live outside the EU,” she says. Now she is looking forward to a productive working environment at the Institute of Psychology at Goethe University Frankfurt.
A portrait photograph of Professor Shing can be downloaded from: www.uni-frankfurt.de/70593429
Caption: Professor Yee Lee Shing recently joined Goethe University Frankfurt as Professor of Developmental Psychology. She brought with her an ERC Starting Grant which will fund research into predictive memory systems. (Photo: Uwe Dettmar)
Further information: Professor Yee Lee Shing, Professor of Developmental Psychology, Institute of Psychology, Tel.: +49(0)69-798-35258, www.entwicklungspsychologie.uni-frankfurt.de
Even apps that are installed but not used can access sensitive personal data
FRANKFURT. More and more applications (apps) for smartphones are available that are able to access personal data without the user’s knowledge. Researchers at the Goethe University Frankfurt have now developed an app which detects data privacy risks and puts users back in control of what their installed apps do.
The unstoppable spread of smartphones brings an increasing number of apps that are on the one hand useful but on the other hand precarious in terms of data privacy, for example in the areas of transportation, e-health, etc. There is meanwhile even the term “smartphone ecosystems” as a consequence of this widespread connectivity. Accordingly, users wanting to use an app are often obliged to reveal their personal data. As a result, data privacy is becoming one of the most important challenges in this rapidly growing market.
“There are companies that sell smartphone users’ personal data to the advertising agencies. Individuals who blindly share photos, videos, email addresses, credit card details or home/work location via insecure apps are also vulnerable to blackmail,” explains computer scientist Majid Hatamian, doctoral researcher at the “Deutsche Telekom Chair of Mobile Business & Multilateral Security” of Goethe University Frankfurt. From his experience, most users are shocked when they discover how much personal information is being passed on without their knowledge and consent.
That is why Hatamian, who has Iranian roots, has developed an app for Android users that shows which personal data are accessed by an installed app, at what time, how often and for what reason. The “Android App Behaviour Analyser (A3)” is a tool that analyses and detects those apps which could misuse personal data. Through extensive experimental analysis, Hatamian was able to show that a considerable number of apps, which were installed but had not been used even once, still passed on and accessed user’s sensitive personal data.
Goethe University Frankfurt (Dr. Jetzabel Serna and Prof. Kai Rannenberg) and RheinMain University of Applied Sciences (Prof. Bodo Igler) were responsible for the project’s scientific coordination. It was financed from the "Privacy&Us" project under the EU’s Marie Skłodowska-Curie programme. The results of the study, which were announced in 2017 at the
14th International Conference on Trust, Privacy & Security in Digital Business (TrustBus 2017), have now been published and are publicly available.
Publication: Hatamian M., Serna J., Rannenberg K., Igler B. (2017) FAIR: Fuzzy Alarming Index Rule for Privacy Analysis in Smartphone Apps. In: Lopez J., Fischer-Hübner S., Lambrinoudakis C. (eds.) Trust, Privacy and Security in Digital Business. TrustBus 2017. Lecture Notes in Computer Science, Vol. 10442. Springer, Cham
Further information: Majid Hatamian, Deutsche Telekom Chair of Mobile Business & Multilateral Security, Faculty of Economics and Business Administration, Westend Campus, Tel.: +49(0)69-798-34662; email@example.com
German Research Foundation funds new Koselleck project at Goethe University Frankfurt: Professor Thomas Ede Zimmermann on the quest for new methods for analysing sentences
FRANKFURT. January 2018 saw the launch at Goethe University Frankfurt of a further Koselleck project funded by the German Research Foundation. The project, headed by professor and linguist Thomas Ede Zimmermann, deals with “Propositionalism in Linguistic Semantics”. Through its Koselleck funding line, the German Research Foundation aims to support researchers with bold ideas who are ready to take risks.
How do we humans understand linguistic content? That sense is not the outcome just of single words is presumably common knowledge. Formal semantics investigate the role played by grammar in imparting meaning. Professor Thomas Ede Zimmermann and his team aim now to investigate the underlying theoretical principles by means of a critical analysis of what is known as the “propositionalist hypothesis”. This hypothesis assumes that any reference to linguistic content is ultimately based on clausal embedding in grammar. More liberal intensionalist approaches, by contrast, build on the assumption that information content in principle corresponds to all types of expression. “We anticipate that the propositionalist hypothesis – depending on how precisely it is defined – will prove either to be trivial for formal reasons or empirically inadequate,” says Zimmermann. Ultimately, the aim is also to find alternatives to propositionalism. Whether this can be achieved remains to be seen. The German Research Foundation has placed a total budget of € 1.25 million at the project’s disposal up until the end of 2022.
What plays an especially important role in the project is the difference between extensional and intensional grammatical constructions. Extensional constructions are characterized by the fact that co-referring names and descriptions within them can be substituted without compromising the accuracy of the overall statement. Relative clauses, which another of Zimmermann’s research groups has been studying in depth for many years, are an example of such extensional constructions. For example, the sentence ‘The conman, who is from Wiesbaden, is on the run’ cannot become incorrect if the word ‘Wiesbaden’ is replaced by ‘Hessen’s capital city’. Attaching object clauses to attitude verbs such as ‘know’ or ‘think’ is an intensional construction: In the sentence ‘Fred knows that the conman is from Wiesbaden’, substituting the place name is not necessarily legitimate because Fred might have wrong ideas (or no idea at all) about Hessen’s capital city. According to Zimmermann, this distinction between extensional and intensional constructions is pivotal: Whilst the first type of construction can be captured by simple set-theoretic means, the second type demands much more sophisticated methods of information processing.
Intensional constructions typically involve (complete or incomplete) sentences, as in the case of object clause attachment mentioned above. According to a highly influential tradition, this is no coincidence: According to propositionalist analyses, intensionality is always a result of clausal embedding, to which apparent counterexamples can be attributed through suitable paraphrases.
In fact, in formal semantics, such constructions are often treated as underlying clausal embedding. The propositionalism project now underway in Frankfurt devotes itself to the general question of the extent to which the propositionalist strategy can be applied to any kind of intensional construction in arbitrary languages.
The project is not, however, confined to detecting and analysing potential counterexamples. According to Zimmermann, the risk - which is a typical characteristic of Koselleck projects - lurks above all in theory development, since previous attempts in this direction have shown that by the use of algebraic coding methods apparent counterexamples can be reformulated in such a way that they fulfil the propositionalist hypothesis at least in letter. What is needed in order to get to the bottom of this is interdisciplinary expertise in the areas of linguistics, logic, and philosophy of language, which the project manager and his (initially) four assistants as well as a whole number of international collaborators are able to contribute.
The Koselleck project is already the fifth at Goethe University Frankfurt. According to the German Research Foundation, the funding programme, which was launched in 2008, “enables outstanding researchers with a proven scientific track record to pursue exceptionally innovative, higher-risk projects”. The programme is named after Reinhart Koselleck who died in 2006. He was one of the most prominent historians of the 20th century and a founder of modern social history in Germany.
Further information: Professor Thomas Ede Zimmermann, Department of Linguistics, Faculty of Modern Languages, Norbert-Wollheim-Platz 1 (Westend Campus), Tel.: +49 (0)69 798-32394, email T.E.Zimmermann@lingua.uni-frankfurt.de; URL: www.Propositionalismus.de
ACE syndrome caused by pathological protein aggregates/Research lays groundwork for causal therapies
FRANKFURT. Mutations in the p63 protein lead to a number of disorders, but none is as severe as the AEC syndrome. Scientists at Goethe University Frankfurt in collaboration with a research group from the University of Naples Federico II have now discovered that this syndrome resembles diseases such as Alzheimer’s, Parkinson’s or ALS more closely than it does other p63-based syndromes. Their results, which were recently published in the scientific journal “Proceedings of the National Academy of Sciences” (PNAS), lay some groundwork for the development of new therapies.
The origin of many diseases lies in genetic abnormalities that result in malfunctions in the proteins they are encoding. A well-known und extensively studied example is p53, the tumour suppressor protein. Inactivation of p53 is one of the first stages in the development of a tumour. Mutations in the homologous protein p63, however, lead to a group of syndromes characterised by defects in embryonic development.
The transcription factor p63 functions in the stem cells of the upper skin (epidermis) and regulates their development and proliferation. Mutations in a certain part of the protein are responsible for the life-threatening disorder ankyloblepharon-ectodermal dysplasia-clefting (AEC), which is characterised, for example, by cleft palate and long-lasting skin erosions similar to severe burns. Some symptoms can be remedied or alleviated through surgery, but so far an approach to treat the cause has not been possible due to a lack of knowledge about the mutated p63 molecules.
The mutations that cause the AEC syndrome cluster in two domains of the p63 protein and do not overlap with those of the other syndromes associated to it. Since these domains are known to be a platform for protein-protein interactions, it has to date been assumed that the disorder is triggered through a loss of those interactions.
“Instead, we were able to show that mutations within p63 expose hydrophobic amino acid sequences that attach to each other in the cell and form large unstructured complexes. This leads to the loss of p63’s function as a stem cell factor,” explains Professor Volker Dötsch from the Institute of Biophysical Chemistry at Goethe University Frankfurt. Similar types of protein aggregates also cause other diseases, such as Parkinson’s, Alzheimer’s or ALS.
A wide variety of biochemical, biophysical and cell biological methods as well as a mouse model of the disorder were necessary to decipher this novel mechanism in detail. A success that was only possible thanks to close and interdisciplinary collaboration with the research group led by Professor Caterina Missero at the University of Naples Federico II. The researchers were also able to show that p63 regains its activity once the formation of aggregates is blocked. The research therefore opens up promising new avenues for treating the causes of the AEC syndrome.
Claudia Russo, Christian Osterburg, Anna Sirico, Dario Antonini, Raffaele Ambrosio, Julia Maren Würz, Jörg Rinnenthal, Marco Ferniani, Sebastian Kehrloesser, Birgit Schäfer, Peter Güntert, Satrajit Sinha, Volker Dötsch und Caterina Missero: Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome, in PNAS early edition, www.pnas.org/cgi/doi/10.1073/pnas.1713773115
A picture can be downloaded from: www.uni-frankfurt.de/70121393
Caption: Child with AEC syndrome.
Photo: Virginia Sybert
Further information: Professor Dr. Volker Dötsch, Institute of Biophysical Chemistry, Faculty of Biochemistry, Chemistry and Pharmacy, Riedberg Campus, Tel.: +49(0)69-798-29631, firstname.lastname@example.org.