Title Promoter Affiliations Abstract "Development of novel TCO probes for pretargeted intracellular PET imaging." "Koen Augustyns" "Molecular Imaging and Radiology (MIRA), Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO), Vienna University of Technology, Medicinal Chemistry (UAMC)" "Radiolabeling of monoclonal antibodies (mAbs) is a powerful preclinical and clinical research tool that finds applications in diagnostic as well as in prognostic and therapeutic settings. Positron Emission Tomography (PET) differs from traditional imaging in that probes known as radiotracers carrying a radioisotope are used to visualize, characterize, and quantify biological processes in vivo. However, despite their attractive properties radiolabeled mAbs have a few important shortcomings. One of the most critical ones is their long circulation time in the body associated with low target to non-target ratios, thus requiring the use of long lived isotopes which yields high radiation dose to the patient. A solution for this problem is offered by pretargeting based on bioorthogonal chemistry. This allows in vivo imaging of the target with superior image contrast and reduced radiation doses. An additional challenge is that many mAbs are internalized upon binding to their target on the cell surface, before the pretargeting reaction. To overcome this issue, this project aims at developing a pretargeted intracellular PET imaging strategy. We will develop novel fluorinated trans-cyclooctene analogues (TCOs) and characterize their potential for pretargeted intracellular imaging using an innovative approach of ""turn-on"" FluoroBOT labeled mAbs. Finally, following optimization of radiochemistry, the 18F-TCO will be used in an in vivo imaging study." "Imaging the link between metabotropic and ionotropic signaling in vivo" "Matthias Schönberger" "Radiopharmaceutical Research" "Cellular communication is a prerequisite for the life of multicellular organisms. Evolution has given rise to a variety of messenger systems that differ in speed and range. The communication between the outside and the inside of a cell is a key interface that is largely orchestrated by transmembrane receptors. This family of communication proteins can be roughly divided into two classes: 1) Metabotropic receptors, which trigger intracellular second messenger signaling cascades and 2) ionotropic receptors, which allow ions to cross the cell membrane. G-protein coupled inwardly rectifying potassium (GIRK) channels present a link between these two communication pathways and will be the focus of this thesis." "In vivo imaging and therapy using labeled antibody derivatives" "Guy Bormans" "Radiopharmaceutical Research" "Glycans play a central role in numerous events in cell-cell recognition, cell communication and cell mobility. Errors in glycan architecture and expression level can lead to pathologies such as cancer. Tumor Associated Carbohydrate Antigens (TACA) are specific glycans that can serve as biomarkers for tumor diagnostics as is already the case for carcinoembryogenic antigen (CEA). This project will focus on the xeno-glycan Neu5Gc (N-glycolylneuraminic acid) and the onco-fetal glycan Globo-H (globoside H type 3 trisaccharide) as new targets for in vivo imaging with theranostic potential. Both glycans, detected on the outer cell membrane in breast, ovarian and gastrointestinal cancer, are in clinical studies as antigen for anti-tumor vaccination. We want to investigate the use of fluorine-labeled small biomolecules for visualization of Neu5Gc and Globo-H expression on tumors. Antibodies are suboptimal for in vivo imaging because they require a relatively long waiting time between injection and imaging, necessitating the use of relatively long-lived radionuclides. Depending on the contrast and the pharmacokinetics, the biomolecules will be examined for targeted radionuclide therapy." "Formulation and processing of probiotic bacteria in a solid oral dosage form for pharyngeal delivery." "Filip Kiekens" "Environmental Ecology & Applied Microbiology (ENdEMIC), Laboratory of Pharmaceutical Technology and Biopharmacy" "Respiratory infections know a high morbidity. Nowadays, patients are treated with over-thecounter products such as decongestives and expectorants. There is also an overuse of antibiotics, which leads to antibiotic resistance. Therefore, a new therapy, based on microbiomemanipulation, is imposed. This research will focus on the improvements for this new therapeutic strategy. The human body consists of many microorganisms lives in symbiosis with each other, resulting in beneficial effects for both. Pathogens can disturb this symbiosis. The homeostasis can be restored by probiotic formulations. They will reinforce the innate immunity. It is the aim of this research to develop a solid oral dosage form for the pharyngeal delivery of probiotic bacteria, which can prevent and treat respiratory infections. Mechanical stress during compression can damage the bacteria, which can result in therapy failure. The aim of this research is to protect the bacteria by choosing the correct formulation and process parameters. This research will be combined with detailed microbiological analysis. The stability of the formulation will be investigated by stability tests. Finally, the efficacy and safety of the formulation will be determined by in vitro tests. Successful results can lead to clinical studies on humans and to new businesses. This can result in a medical and economical progress.." "Installing a center of excellence in the Central-Eastern region of Cuba to enhance production and research on bioactive plants." "Paul Cos" "Medicinal Chemistry (UAMC), Natural Products and Food - Research and Analysis (NatuRA), Laboratory for Microbiology, Parasitology and Hygiene (LMPH)" "This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract. The aim of the project is to set-up a center of scientific excellence in the Central-Eastern region of Cuba for traditionally used bioactive plants and their metabolites." "Active Filtering Technology for Algae harvesting (ACTIFALG)." "Serge Tavernier" "Biochemical Wastewater Valorization & Engineering (BioWaVE)" "A functional prototype of an algae harvester will be built and tested in real life conditions. The first target is to optimize the actual concept (dimensions, layout, choice of materials and physical parameters). The second target is to study in detail the operational window and the global costs (hardware and operational cost) and compare them with actual algae harvesters." "Modulation of glycolytic flux as a new approach for treatment of atherosclerosis and plaque stabilization: a multidisciplinary study (MOGLYNET)." "Guido De Meyer" "Physiopharmacology (PHYSPHAR)" "The mission of MoGlyNet is to define a joint doctorate educational training model in Drug Discovery and Development where Academia and Industry join their forces for:- creating a common platform of knowledge and language for early stage researchers (ESR) working in the Drug Discovery and Development area aiming to convey complementary pharma-skills- exploiting this platform to train a new generation of cutting-edge researchers and professionals highly attractive for employment by the European Pharma-industry- establishing structures for long-term cooperation, strengthening the relationships among the leading Universities and Pharma-enterprises and to continuously develop the research training platform that European industry relies on." "Development of an integrated strategy to characterize new lead compounds based on natural pro-drugs and their metabolites." "Luc Pieters" "Toxicological Centre, Natural Products and Food - Research and Analysis (NatuRA)" "Many natural products are pro-drugs that are metabolized and activated after oral administration. Nevertheless this aspect is usually overlooked when searching for new lead compounds for therapeutic agents. In this project Filipendula ulmaria (meadowsweet) and Herniaria hirsuta have been selected as case studies for the characterization of new leads for anti-inflammatory drugs, and drugs for nephrolithiasis. An LC-MS and 1H-NMR platform will be used for the fast metabolomic profiling of plant extracts, prepared using comprehensive extraction methods to cover the full range of constituents. Secondly, the platform will be extended with a dialysis model simulating human gastro-intestinal (GI) metabolization, which will be applied to activate potential pro-drugs. In addition, the dialysate containing the GI metabolites will be treated with microsomal S9 fractions to mimic liver metabolization. The resulting metabolized samples (before and after S9 treatment) will be profiled in the same LC-MS and 1H-NMR platform, and compared with the original profiles. At the same time all extracts and metabolized extracts will be pharmacologically evaluated in a range of in vitro assays related to anti-inflammatory and anti-nephrolithiasisproperties. Pharmacological and chromatographic / phytochemical data will be analyzed in a metabolomics approach using multivariate data analysis in order to characterize the pharmacologically active constituents and their metabolites as new lead compounds." "Expanding the detection window in forensic toxicology: hair and nail analysis." "Toxicological Centre" "This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract." "Creation of a preclinical platform at the UA for testing novel therapeutic approaches against ocular surface diseases." "Paul Cos" "Laboratory of Pharmaceutical Technology and Biopharmacy, Medical Biochemistry, Medicinal Chemistry (UAMC), Laboratory for Microbiology, Parasitology and Hygiene (LMPH)" "Ocular Surface diseases (OSD) such as dry eye syndrome (DES) show an estimated prevalence between 15 and 29%. The only FDA approved and on subscription dry-eye treatment is cyclosporine 0.05% (Restasis®), but this formulation is not available in the EU. Novel therapies for OSD are therefore needed. The expertise within ADDN fosters a unique opportunity to set up a preclinical platform on OSD leading to an increased collaboration with industrial partners."