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Country: Belgium


196 Projects, page 1 of 40
  • Funder: European Commission Project Code: 835243
    Overall Budget: 2,499,380 EURFunder Contribution: 2,499,380 EUR

    Fertilization is essential for a species to survive. Mammalian sexual reproduction requires the fusion between the haploid gametes sperm and egg to create a new diploid organism. Although fertilization has been studied for decades, and despite the remarkable recent discoveries of Izumo (on sperm) and Juno (on oocytes) as a critical ligand:receptor pair, due to the structure of Izumo and Juno, it is clear that other players on both the sperm and the oocytes must be involved. While the focus of our laboratory over the years has been in understanding apoptotic cell clearance by phagocytes, we accidentally noted that viable, motile, and fertilization-competent sperm exposes phosphatidylserine (PtdSer). PtdSer is a phospholipid normally exposed during apoptosis and functions as an ‘eat-me’ signal for phagocytosis. Further, masking this PtdSer on sperm inhibits fertilization in vitro. Based on additional exciting preliminary data, in this ERC proposal, we will test the hypothesis that PtdSer on viable sperm and the complementary PtdSer receptors on oocytes are key players in mammalian fertilization. We will test this at a molecular, biochemical, cellular, functional, and genetic level. From the sperm perspective — we will ask how does PtdSer changes during sperm maturation, and what molecular mechanisms regulate the exposure of PtdSer on viable sperm. From the oocyte perspective — we will test the genetic relevance of different PtdSer receptors in fertilization. From the PtdSer perspective — we will test PtdSer induces novel signals within oocytes. By combining the tools and knowledge from field of phagocytosis with tools from spermatogenesis/fertilization, this proposal integrates fields that normally do not intersect. In summary, we believe that these studies are innovative, timely, and will identify new players involved in mammalian fertilization. We expect the results of these studies to have high relevance to both male and female reproductive health and fertility.

  • Funder: European Commission Project Code: 713758
    Overall Budget: 150,000 EURFunder Contribution: 150,000 EUR

    Angiogenesis, the growth of new blood vessels, contributes to major pathologies such as blinding ocular disease, inflammation and cancer. Blocking angiogenesis has therefore become a major field of research and an attractive therapeutic strategy. Current anti-angiogenic therapies focus on blockade of pro-angiogenic factors, such as VEGF. However, in cancer, insufficient efficacy, resistance and toxicity restrict the success of anti-VEGF agents. There is thus an urgent unmet need for novel anti-angiogenic strategies. In our ERC Advanced research grant (ECMetabolism), we developed an entirely novel anti-angiogenic concept and strategy, based on targeting key metabolic pathways in endothelial cells (ECs), cells lining blood vessels. More in particular, we identified - for the first time - that PFKFB3, a key glycolytic regulator, as a novel and promising target for anti-angiogenic therapy. Our findings show that glucose metabolism determines vessel sprouting and that lowering glycolysis only partially and transiently (by blocking PFKFB3) sufficed to inhibit pathological angiogenesis without causing systemic effects. In this ERC proof of concept project, PFKFBLOCK, we aim to develop lead small molecule compounds, blocking PFKFB3, and evaluate their potential to block pathological angiogenesis. Currently, no specific and orally available PFKFB3 blocker exists underscoring the value of our proposal and the necessity to develop such blocker for therapeutic applications. Through collaboration with a drug discovery unit we will identify lead molecules with novel intellectual property potential. Those lead compounds will be validated in relevant in vivo models and considered to be patented. The ultimate goal of this project is to get the best PFKFB3 inhibitor in clinical trials.

  • Funder: European Commission Project Code: 897918
    Overall Budget: 166,320 EURFunder Contribution: 166,320 EUR

    Plants produce arrays of specialized metabolites that are crucial for plant development, defense and interactions with the ever-changing environment. Discovery of metabolites and metabolic pathways by dissecting the underlying genetic basis is an important challenge, not only to increase our understanding of life, but also to provide indispensable applications for humans such as pharmaceuticals. In this project we will investigate the occurrence and biosynthesis of the 2,5-dihydrochorismates, a novel metabolic class that was recently discovered by the host group in the plant model Arabidopsis (unpublished). Notably, chemically synthesized 2,5-dihydrochorismate and analogues have been shown to be potent in vitro inhibitors of chorismate-utilizing enzymes. This inhibitory activity hints to a potential biological role for 2,5-dihydrochorismates in regulating the flux through these pathways, opening perspectives for applications. The direct objective of my project is to unravel the biosynthetic pathway of 2,5-dihydrochorismates. We therefore aim i) to structurally identify additional pathway intermediates and sinks via LC-MS based metabolite profiling and purification followed by NMR, ii) to test whether chorismate is a precursor of the pathway by feeding plants with Stable Isotope Labeled chorismate, followed by analyzing the MS fragmentation spectra of the labeled molecules, iii) to investigate the role of an operon-like gene cluster involved in the biosynthesis of 2,5-dihydrochorismates via reversed genetics, and iv) to obtain insight in the in planta role of 2,5-dihydrochorismate by feeding experiment followed by metabolic profiling. My experience in reversed genetics and enzyme kinetics in specialized metabolism in rice make me well suited to bring this project to success. My prime objective is to strengthen my skills in metabolite profiling, pathway discovery and structural elucidation, to become an independent plant scientist in plant specialized metabolism.

  • Funder: European Commission Project Code: 101107007
    Funder Contribution: 175,920 EUR

    It is common knowledge that an ethernet connection is safer than a wireless connection, and cellular organelles share this approach. To communicate directly among each other, organelles are thought to use Membrane Contact Sites (MCS), the “optical fibers” at the intracellular level. Organelles are in a prime position to sense and communicate stress signals due to their tight integration into the cell’s metabolic networks. Inter-organelle communication is thus crucial to pass on the message to coordinate cellular stress responses and maintain homeostasis. I hypothesise that MCS allow fast and efficient communication of stress signals between intracellular organelles (e.g. mitochondria and ER) to coordinate the cellular stress responses. However, the organelle tethering proteins, the stimuli driving MCS formation and the signalling molecules mediated through these MCS remain elusive in plants. In INTERCOM, I will characterise ER-mitochondria communication in response to stress in Arabidopsis thaliana. For that, I will leverage the host lab’s previously established ER-mitochondria communication model system and establish a proteomic screening setup to identify novel proteins involved in ER-mitochondria MCS in plants. In addition, I will develop a high-throughput platform to study inter-organelle interactions in vivo and to identify stimuli driving MCS dynamics. Finally, I will employ genetically encoded biosensors to pinpoint ROS and calcium inter-organelle signalling events. To reach my goal, I will combine my expertise in intracellular signalling and bioimaging with cutting-edge interactomics, live-cell imaging and high-content technologies available at the host institute. This innovative and interdisciplinary approach will allow me to shed light on plant inter-organelle communication, a field still in its infancy in plant biology with the potential to pave the path for the biotechnological engineering of plants more resilient to harmful environmental conditions.

  • Funder: European Commission Project Code: 101152131
    Funder Contribution: 191,760 EUR

    Unlocking the mysteries surrounding nutrient fate within the human body has remained an enigmatic pursuit. Our organs and tissues crave specific nutrients, especially in physiological and pathological conditions. Yet, the intricate journey these nutrients embark upon within our bodies remains largely unclear. The aim of my ambitious project is thus to create an innovative chemical-spatial workflow capable of (1) providing the anatomical coordinates of nutrients of interest across tissues (and organs) and (2) understanding the biochemical route these nutrients undergo in the respective tissue areas of the target organ. For this, I will use a complementary approach relying on advanced techniques such as tracer metabolomics, mass spectrometry imaging (MSI) and Stimulated Raman spectroscopy (SRS). I will benchmark this technological platform onto a model of acute kidney injury (AKI) to identify and localize the predominant biochemical pathways. The amalgamation of SRS and MSI with tracer metabolomics is groundbreaking given the current technological landscape and provides an innovative and feasible solution to the posed challenge.


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