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University of Tübingen

University of Tübingen

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381 Projects, page 1 of 77
  • Funder: EC Project Code: 101117404
    Overall Budget: 1,499,920 EURFunder Contribution: 1,499,920 EUR

    In recent years, rapid developments in the field of ancient metagenomics, enabled through advances in genomic sequencing and ancient DNA retrieval, have provided temporal transects of microbial diversity and have paved the way for studying human-pathogen interactions, on the biological and cultural dimensions, far earlier than the written historical record. With these tools at hand, PROTOPEST will utilise a timely opportunity for investigating the impact of infectious disease epidemics on prehistoric human societies. The project will be centred on the 2nd millennium BCE, a period of large-scale socio-cultural transformations witnessed differentially across the archaeological records of Europe, Near East and Asia. Until now, studies have focused on environmental changes, economic shifts, warfare and human migration to explain these phenomena. Crucially, the 2nd millennium bears the earliest textual evidence of infectious disease epidemics ever identified, yet, their possible contribution to observed transformations, as well as their trans-regional impact beyond textual descriptions, remain largely unexplored. PROTOPEST will produce extensive ancient metagenomic, pathogen genomic and human genomic datasets, generated from human and animal remains across key regions of Europe, the Near East and Central Asia. Co-analysed alongside cultural, isotopic, paleodemographic and palaeopathological information, these data will be used to expose the unknown landscape of Middle/Late Bronze Age epidemics across a large geographical expanse. Our unique multidisciplinary framework will define indicators of prehistoric community responses to infectious disease outbreaks, and reveal how pathogens emerged and disseminated within and across human populations. In this capacity, PROTOPEST will provide a deep evolutionary and cultural framework for empirically examining the diachronic challenges that pathogens have posed on human societies, to gain a more holistic view on human prehistory.

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  • Funder: EC Project Code: 101069246
    Funder Contribution: 150,000 EUR

    RNA base editing is a promising approach to manipulate genetic information in a transient and dosable way, which breaks new ground in basic Life Science research and drug discovery. In a preceding ERC CoG action, we have engineered the SNAP-ADAR tool, which allows for the particularly precise, efficient and programmable adenosine-to-inosine RNA base editing. However, the broad usage of this tool is somewhat hampered by the need for designing the chemically modified guideRNAs, which currently includes some peptide bond-forming chemistry and nucleic acid gel purification. In this PoC action, we aim to simplify the tool to make it available for a larger section of the Life Science community. Specifically, we aim to simplify the chemistry and the compounds to such an extent that a SNAP-ADAR kit is obtained, which enables the Life Scientist to perform the required chemistry without special equipment or chemistry skills. Furthermore, the kit would include a reliable and simple protocol to perform efficient and precise editing reactions in mammalian primary cells. Profit could particularly be generated from the selling of the chemically stabilized guideRNAs. We envision that the product would find application in the modulation of protein function like signaling cues and metabolic pathways and may foster the target screening and target validation in drug discovery efforts, which are currently ongoing in the field of RNA base editing. The action also contains an analysis of the IP landscape and - at the later stage of the action - we aim to involve industrial partners for commercialization.

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  • Funder: EC Project Code: 307320
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  • Funder: EC Project Code: 256502
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  • Funder: EC Project Code: 647328
    Overall Budget: 1,808,200 EURFunder Contribution: 1,808,200 EUR

    Enzymatically active RNA-guided proteins, like the RNA-induced silencing complex (RISC), are particularly versatile tools for the rationally programmed manipulation of genetic information. After successful re-addressing of various natural RNA-guided machineries it is now time to tackle the engineering of novel, user-defined tools. With this respect we have recently achieved the engineering of an RNA-guided adenosine-to-inosine RNA editing machinery. Since inosine is biochemically read as guanosine, A-to-I editing alters genomic information on the RNA-level and may potentially allow for the manipulation of RNA processing or protein function. We have already achieved to apply our RNA editing approach for the repair of several missense and nonsense point mutations on reporter and disease-related genes in vitro and demonstrated its applicability in mammalian cell culture. Now, we want to push the method further towards application. To enable editing in oocytes, primary cells and neurons, we will establish to deliver the editing tool by lentiviral vectors and stabilized mRNAs. We further aim to create cell lines expressing the artificial editing machinery under conditional control. We will repair reporter genes in developing worm oocytes, and we want to reconstitute mutations that cause neuro-diseases. We also wish to establish new features including photocontrol and the application of editing to steer protein localization. If successful, site-directed RNA editing will enable us to manipulate RNA and protein function in a yet unprecedented way. The ready introduction of point mutations into mRNAs without the need for genomic engineering may dramatically facilitate the study of protein function, disease mechanism and may even allow for the treatment of diseases based on personalized genetic information.

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