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Country: Germany


2 Projects, page 1 of 1
  • Funder: European Commission Project Code: 101046941
    Overall Budget: 2,665,560 EURFunder Contribution: 2,665,560 EUR

    Many bacteria that cause infectious diseases develop resistance to not only the primary antibiotic treatments available in the clinic but also to drugs of last resort which often require long treatment periods and come with significant side effects. At the same time many promising lead compounds with high activity and wide therapeutic windows have failed to progress to clinical trials due to poor solubility, protein absorption or other difficulties in formulation (e.g. low drugability). LeadtoTreat proposes a new solution to these challenges by introduction of a platform for future infection treatment enabling targeted delivery of novel lead compounds with low drugability as well as synergistic combinations of antibiotics and potentiators in a nano-formulation. A novel dual targeting approach, with both direct targeting toward the pathogenic bacteria as well as to areas of inflammation will be employed. This platform technology will be demonstrated by converting a highly active, but insoluble and protein binding, novel compound into targeted nano-formulations for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections with proven in vivo and in vitro safety. Furthermore, LeadtoTreat aims to identify novel synergistic combinations of antibiotics and potentiators and convert these into highly active targeted nano-formulations for treatment of MRSA infections. LeadToTreat will have significant impact on the future treatment of microbial infections, by demonstrating a pathway to co-delivery of synergistic combination of existing antibiotics as well a path way to revitalize the huge library of abandoned low-drugability lead compounds. From an innovation perspective, it is expected to also develop broadly applicable targeting tools (for MRSA, and roadmap for other indications). The project will be managed by SINTEF (Norway) involving Narodowy Instytut Lekow (National Medicine Institute, NMI, Poland) and NanoTag Biotechnologies GmbH (NTB, Germany).

  • Funder: European Commission Project Code: 964016
    Overall Budget: 3,695,980 EURFunder Contribution: 3,695,980 EUR

    The key principle of biological imaging is specific labeling. The protein of interest is revealed by tagging with fluorophores, either by genetic encoding, using green-fluorescent-protein (GFP) variants, or by affinity labeling, using antibodies. This procedure has been successful for several decades, but has the great disadvantage that each protein needs to be tagged individually: specific antibodies are needed for each and every protein. This limitation stops imaging from becoming a high-throughput “omics” approach. We propose to change this here, through an imageomics approach based on a combination of probe development and nanoscale imaging. We will develop affinity probes that bind with high specificity not to specific proteins, but to amino acid sequences (peptides) that are present in more than one protein. We will choose 20-40 such peptides, in a fashion that ensures that virtually every protein in the human proteome contains a specific subset of the peptides. We will then develop nanobodies that bind to each of these peptides. We prefer nanobodies to antibodies, based on their small size and optimal penetration into biological samples. We will then use the nanobodies to label biological samples, and we will image them at the nanoscale, with a resolution that is sufficient to reveal single proteins. By applying the nanobodies in a combinatorial fashion, we will “read” the sequence of each protein in the preparation, which will result in an image of its whole proteome. We will start by applying this approach to 2-dimensional samples, such as fluids adsorbed to coverslips. This will lay the foundation for future diagnostic studies for a variety of human diseases, based on human fluids such as plasma or cerebrospinal fluid. In a later stage, we will proceed to analyze cells and tissues, by generating 3-dimensional proteomic images. This approach will make antibody-based imaging, blotting and diagnostics obsolete, and has therfore an immense potential.

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