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LUNDS UNIVERSITET

Country: Sweden

LUNDS UNIVERSITET

756 Projects, page 1 of 152
  • Funder: EC Project Code: 101043587
    Overall Budget: 1,999,440 EURFunder Contribution: 1,999,440 EUR

    Gliomas are the most common brain tumors and the highest-grade glioma, glioblastoma (GBM), is arguably the most aggressive tumor type, with no long-term survivors. Patients with GBM are treated with radiotherapy, chemotherapy, surgery, and tumor treating fields. Despite initial response all tumors recur as incurable lesions; there is an urgent need for novel therapeutic approaches for this patient group. The majority of GBMs recur within the treatment field receiving high-dose radiotherapy during treatment of the primary tumor; the recurrent tumor thus forms in an irradiated microenvironment. Despite the fact that it is the recurrent tumor that ultimately kills the patient and that the majority of new therapeutic agents for GBM are tested clinically in the recurrent setting, the majority of experimental models and clinical materials for drug discovery are based on primary disease. Recent advances established a central role for the tumor microenvironment in determining the therapeutic response of GBM cells, and our lab demonstrated that standard of care radiotherapy of the primary tumor can shape the microenvironment to generate tumor-supportive conditions in the recurrent tumor; These findings suggest that there is untapped potential in targeting the irradiated microenvironment. This proposal aims to explore and exploit the recurrent brain tumor microenvironment by i) consolidating the contribution of the irradiated brain tumor microenvironment to GBM resistance by integrating spatial transcriptomics, single cell RNA sequencing, and multiplexed immunohistochemistry from state-of-the-art murine and human models of GBM treatment and recurrence, and ii) discovering and targeting novel therapeutic targets unique to the post-radiotherapy brain tumor microenvironment by high-throughput phenotypic screening, with the ultimate goal of exploiting reversible stromal radiation responses and leverage novel therapeutic opportunities unique to the irradiated brain.

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  • Funder: EC Project Code: 236106
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  • Funder: EC Project Code: 252988
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  • Funder: EC Project Code: 101078476
    Overall Budget: 1,657,190 EURFunder Contribution: 1,657,190 EUR

    Living without oxygen is challenging. To live in low-oxygen environments, some microbes exchange nutrients allowing for a division of labor among individuals in a process called ‘syntrophy’. Such interactions are often a pre-requisite for prokaryotes living in these environments. Whether syntrophy is necessary for the survival of microbial eukaryotes (protists) is unexplored and yet, critically important to discerning the roles of eukaryotes in nature and how eukaryotic cells adapt to live without oxygen. TAngO2 will test the hypothesis that syntrophic partnerships allow eukaryotes to thrive in anaerobic environments and underpin the evolution of key eukaryotic cell biological characteristics. This will be accomplished using state-of-the-art genomic, computational, and experimental approaches. I will discover genes essential for interactions between a model protist and its ectosymbiont using massively-parallelized transposon mutagenesis. This will discern the molecular mechanisms, metabolic interplay, and selective forces dictating eukaryote:prokaryote interactions. I will deliver metagenomes of cultured anaerobic eukaryote:prokaryote consortia predicted to be engaging in syntrophic interactions. This will drastically expand our knowledge of the biodiversity of eukaryotic genomes and microbial interactions from low-oxygen environments. I will interrogate the frequency and diversity of syntrophy in eukaryotes by simultaneously sequencing the genomes and transcriptomes ofindividual protist cells and their microbiota sampled from nature. This will provide the first elucidation of what communities co-exist with natural anaerobic protists. Understanding how syntrophic interactions have influenced eukaryotic cell biology will reveal hidden connections in the complicated functional networks of the eukaryotic cell. TAngO2 will open research avenues by bridging the fields of evolutionary cell biology and microbiology to understand ancient and recent symbiotic

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  • Funder: EC Project Code: 101078349
    Overall Budget: 1,499,920 EURFunder Contribution: 1,499,920 EUR

    Advances in tracking technology during the last decade have shown that migratory birds have the capacity to fly longer and faster than we previously thought was possible. Yet, we do not know how birds perform these seemingly impossible travels as it previously only was possible to record spatiotemporal patterns. The overall aim of this project is to reveal constraints and the behavioural and physiological adaptations that has evolved to overcome them, thus making the extreme performances of migratory birds possible. This goal will be met by using novel tracking devices, multisensor data loggers, that in addition to spatiotemporal patterns also record behaviour, including flight altitudes, temperature and detailed timing of flights and stopovers during the entire migration cycle. The few multisensor tracking studies carried out to date have provided hints of stunning new insights, and seriously challenged previously assumed limits on peak flight altitudes, in-flight changes of altitudes, and duration of individual flights. In particular, I have together with colleagues discovered a totally unexpected altitudinal behaviour: some bird species change their flight altitude between night and day, and fly at extremely high altitudes during the day (up to 6000-8000 m). But what makes a migratory bird fly as high as Mount Everest, even when there are no mountains to cross? By launching an extensive multisensor data logging programme, combined with wind tunnel experiments and field studies, the proposed project will change our understanding of the possibilities and limitations of bird migration. This will be done by disentangling the causes and consequences of bird’s altitudinal behaviour, the flexibility, timing and duration of migratory flights (if birds only use diurnal or nocturnal flights, if they prolong flights to last both day and night or even fly nonstop between wintering and breeding grounds), and the costs and consequences of these seemingly extreme behaviours.

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