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Country: Netherlands
243 Projects, page 1 of 49
  • Funder: EC Project Code: 851368
    Overall Budget: 1,499,960 EURFunder Contribution: 1,499,960 EUR

    There is a considerable shortage of deceased donor kidneys. Hence, more organs of marginal quality need to be considered for transplantation. Transplant centers are increasingly utilizing ex vivo normothermic machine perfusion to better preserve donor kidneys prior to transplantation. Little is known about molecular pathways that are active while the organ is perfused ex vivo. Also, there is hardly any data on which molecular processes are relevant to assess organ quality during perfusion. I aim to determine the molecular mechanisms of ex vivo kidney perfusion prior to renal transplantation in order to develop breakthrough pre-transplant perfusion-based diagnostic markers that can indicate kidney transplant outcomes. First, a series of normothermic ex vivo porcine kidney perfusions will be conducted with repeated tissue and perfusate sampling. Ex vivo measurements will be contrasted with the contralateral kidney that remains in vivo. Genomics, transcriptomics, proteomics and metabolomics, as well as ex and in vivo magnetic resonance imaging followed by radiomics will be employed. Distinct molecular pathways will be identified which characterize an ex vivo perfused kidney, compared to the organ’s behaviour in vivo. Second, the discovered molecular pathways will be validated for human donor kidneys by performing ex vivo perfusions of discarded human organs followed by the same multi-omics approach. Finally, a prospective clinical study will be conducted with human kidneys that are perfused ex vivo prior to transplantation. With artificial intelligence analysis, tissue and perfusate multi-omics measurements and standard clinical variables will be associated with transplant results, to create advanced prediction models for post-transplant outcome. The high gain of my project will be a better understanding of molecular mechanisms during ex vivo kidney perfusion and advanced, personalized pre-transplant prediction models for post-transplant outcome.

  • Funder: EC Project Code: 713660
    Overall Budget: 3,348,480 EURFunder Contribution: 1,674,240 EUR

    The Microbes in Health and Disease research programme at the University Medical Center Groningen (UMCG) proposes the Doctoral Training Programme PRONKJEWAIL (‘a real gem’) in the field of hospital care and infection. The specific training objective is ‘protecting patients with enhanced susceptibility to infections’. PRONKJEWAIL will recruit 16 international ESRs, who will be trained in research, transferable skills, and network and capacity building. They will be guided by experienced supervisors from the departments of Medical Microbiology, Internal Medicine, Intensive Care, Clinical Pharmacy and Pharmacology, Rheumatology and Immunology, Surgery, Cell Biology, and Pharmacoepidemiology and Pharmacoeconomics at the UMCG. 26 partner organisations, including 14 private sector partners, are committed to support ESR training via mentoring, courses and secondments. Research training builds on four Pillars: 1) vaccines and primary prevention; 2) personalized detection and infection prevention; 3) iatrogenic influence on the microbiome and 4) personalized therapy/stewardship. Each Pillar integrates fundamental, translational and clinical/epidemiological training projects. The high exposure to fundamental, translational and clinical research in academia and industry will increase the ESRs future problem-solving capabilities. Further, ESRs will learn to value mobility through internships at international partner organizations. By providing an excellent scientific working environment PRONKJEWAIL will directly impact on hospital care and, ultimately, it will contribute to enhanced public health. By providing excellent training, PRONKJEWAIL will develop new talent within the next generation of medical researchers thereby strengthening the European Research Area.

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  • Funder: EC Project Code: 310765
  • Funder: EC Project Code: 715772
    Overall Budget: 1,499,880 EURFunder Contribution: 1,499,880 EUR

    The role of intestinal bacteria in human health and disease has been intensively studied; however the viral composition of the microbiome, the virome, remains largely unknown. As many of the viruses are bacteriophages, they are expected to be a major factor shaping the human microbiome. The dynamics of the virome during early life, its interaction with host and environmental factors, is likely to have profound effects on human physiology. Therefore it is extremely timely to study the virome in depth and on a wide scale. This ERC project aims at understanding how the gut virome develops during the first year of life and how that relates to the composition of the bacterial microbiome. In particular, we will determine which intrinsic and environmental factors, including genetics and the mother’s microbiome and diet, interact with the virome in shaping the early gut microbiome ecosystem. In a longitudinal study of 1,000 newborns followed at 7 time points from birth till age 12 months, I will investigate: (1) the composition and evolution of the virome and bacterial microbiome in the first year of life; (2) the role of factors coming from the mother and from the host genome on virome and bacterial microbiome development and their co-evolution; and (3) the role of environmental factors, like infectious diseases, vaccinations and diet habits, on establishing the virome and overall microbiome composition during the first year of life. This project will provide crucial knowledge about composition and maturation of the virome during the first year of life, and its symbiotic relation with the bacterial microbiome. This longitudinal dataset will be instrumental for identification of microbiome markers of diseases and for the follow up analysis of the long-term effect of microbiota maturation later in life. Knowledge of the role of viruses in shaping the microbiota may promote future directions for manipulating the human gut microbiota in health and disease.

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  • Funder: EC Project Code: 101001678
    Overall Budget: 1,999,680 EURFunder Contribution: 1,999,680 EUR

    Individual response rates to drugs that are widely prescribed to treat common diseases are typically in the range of 50-75%, yet the slow progress and high costs associated with new drug development do not meet the urgent need for new treatment options, particularly given the rapidly increasing burden of chronic diseases. This ERC project tackles this pressing issue by defining the impacts of the gut microbiome and genetics on drug metabolism, ultimately enabling personalized approaches that enhance efficacy and safety of already marketed drugs via microbiome modulation. I will start with 23 common drugs used to treat chronic cardiometabolic and psychiatric disorders that threaten public health. The project will address important technical and clinical challenges in three innovative parts: 1) a population-based cohort study using the unique LifeLines-10K cohort to build sophisticated models that take genetic, microbial and lifestyle/health factors into account to improve prediction of drug metabolism; 2) pharmacokinetics analyses using innovative, personalized organ-on-a-chip to better understand causality and mechanism; and 3) an intervention trial using probiotics to achieve greater drug efficacy through modulation of the gut microbiome. In particular, the project will deliver microbiome-targeting solutions to improve the efficacy and safety of one or two drugs and a next-generation drug-testing model that uses an innovative organ-on-a-chip system to mimic metabolic flow along the gut-liver axis while taking an individual’s genetics and gut microbiome into account. This project will lay the foundation for major advances in personalized medicine through: (i) better prediction of individual drug metabolism, which will aid therapeutic decision-making; (ii) better understanding of genetics-microbiome interactions in drug metabolism; and (iii) greater drug efficacy through modulation of the gut microbiome.

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