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.

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.

Glaucoma is the most common age-related neurodegenerative eye-disease in western society and one of the four major blinding eye diseases (cataract, macular degeneration, glaucoma, and diabetic retinopathy). Glaucoma is characterized by a progressive loss of retinal nerve cells. The early changes are often unnoticed by the patient. If untreated or detected too late, glaucoma will end up in blindness, yielding a profound loss of quality of life for the individual and major costs to society. In Europe, there are approximately 3 million people with glaucoma. They all need chronic medical care and, despite of that, approximately 15% of them will become blind during their lifetime. Increasing our knowledge on glaucoma and the aging visual system in general has tremendous potential for innovation in glaucoma care and can thus positively impact the future of millions of European citizens : 1) it enables the development of new tools for the early detection of glaucoma; 2) it can inspire the development and implementation of new treatments; 3) contributes to our understanding of the relationships between various neurodegenerative diseases, and 4) contributes to improving healthy aging in general. Given the vast complexity of the disease, we need researchers that are deeply knowledgeable about glaucoma and intimately familiar with the many different techniques required to study all aspects of glaucoma and the aging visual system: from functional test to anatomy, from gene to ganglion cell, from retina to brain. Generally, knowledge – and thus training – is fragmented and researchers that have been broadly trained are only scarcely – if not at all – available at present. To overcome this, EGRET – the European Glaucoma Research Training Program – will aim its efforts at teaching young researchers in how to acquire and apply new quantitative knowledge on the aging visual system in health and disease (specifically glaucoma).

Reactive Oxygen Species (ROS)/ free radicals (FR) in cells have a very complicated role in viral infections. While some researchers point toward their usefulness in mediating viral infections, others conclude the exact opposite and claim that there are detrimental effects. To probe deeper into virus pathogenesis and improve anti-viral therapy, cellular FR - viral infection kinetics which potentially depends on virus, cell/animal model, type of reactive species, etc. needs to be investigated with high spatiotemporal resolution. However, all the traditional methods capable of detecting FR have limitations when real-time, long-duration, high resolution measurements are to be conducted within a small sample volume (inside of a cell). Recently, diamond magnetometry was proposed to study cellular FR with unparalleled sensitivity, resolution, and the possibility of real-time long-duration measurements. In this highly interdisciplinary collaborative research, I aim to establish this technique in studying cellular FR- viral infections kinetics. As a model system I will investigate the host cell FR response upon Sindbis virus (SINV) infection with high spatiotemporal resolution. FR response will be quantified via measuring T1 relaxation time of Nitrogen Vacancy centers in fluorescent nanodiamonds (FNDs). Furthermore, I intend to highlight the potential of diamond magnetometry in clinical diagnostics and drug development by demonstrating the FR detection in synovial fluid of arthritis patients (outcome of SINV infection) and detecting cells’ FR response to anti- oxidants. Upon successful completion, I will not only have elucidated the interplay of FR and SINV infections but also underscored the potential of diamond magnetometry in fundamental virology, infection biology, clinical diagnostics and pharmaceutical industry. This research strongly aligns with two work programs within Horizon 2020 focused on health (SC1-BHC) and nanotechnology- biotechnology (DT-NMBP).