Press releases – February 2018

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 20^th 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

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.

Publication:

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, vdoetsch@em.uni-frankfurt.de.