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Closing date: July 17
A novel stRatEgy to improve STRomal health in chronic obstrUCTive pUlmonaRy diseasE (RESTRUCTURE-COPD).
The postdoc will be working on an Public-Private Partnership Allowance grant from LongFonds and Health~Holland (Top Sector Life Science and Health).
COPD is characterized by irreversible lung damage, leading to progressive loss of lung function. Novel regenerative treatments are urgently needed. Human lungs contain stem cells capable of tissue regeneration that reside in their local microenvironment (niche), composed of stromal cells and extracellular matrix. Mesenchymal stromal/stem cells (MSCs) are a key stromal element, supporting alveolar regeneration via paracrine mechanisms. Accumulating evidence indicates that interactions in the COPD microenvironment are disturbed, impeding adequate lung tissue repair. Importantly, we recently observed that MSCs from COPD lungs are compromised in the secretion of critical regenerative factors. We propose that restoring the interaction between MSCs and the microenvironment will reintroduce MSC’s regenerative factors (e.g. HGF, FGF10, exosomes), driving repair of damaged lung tissue. We hypothesize that controlled and local delivery of lacking components will augment the regenerative efficacy of native MSCs in COPD lungs. We will achieve this using an innovative micromaterial-based approach to stimulate lung regeneration. We will produce nanoparticle-laden microgels with variable stiffness and composition, and evaluate effects on viability, metabolic activity and trophic mediation of MSCs in vitro as well as their interaction with decellullarized COPD lung tissue. Regenerative compounds have been selected based on our recently concluded Longfonds project, and can be updated by findings from our ongoing large consortium project P4O2 (precision medicine for more oxygen) and international consortia in this field. These factors will be laden into in-house available nanoparticles. Their effectiveness will be studied using our recently developed lung organoid models, recapitulating critical aspects of alveolar regeneration. Local delivery will be assessed by determining the microgel’s biodistribution and its action in ex vivo models, including ovine lungs and human precision-cut lung slices.
Techniques to be used will be culture of MSCs, their effectiveness in organoid models using human lung cell lines and primary cells, qPCR, flow cytometry, ELISA, immunofluorescent staining, ex-vivo lung perfusion, precision-cut lung slices, in vitro evaluation of nanoparticles, generation and characterization of hydrogels, incorporation of compounds into hydrogels.
The postdoc will be working within the department of Pathology & Medical Biology (PMB) of the University Medical Center Groningen, laboratory of Experimental Pulmonology and Inflammation Research (EXPIRE). Within PMB, multiple renowned research groups work on pathophysiological damage and repair processes, using translational and multi-omic approaches (transcriptomics e.g. single cell RNA sequencing, proteomics etc), and state-of-the-art cellular and molecular techniques, to obtain insights into novel therapeutic strategies. The research will be embedded within the Groningen Research Institute for Asthma and COPD (GRIAC), a multidisciplinary and highly translational research institute performing fundamental and applied patient-related research with the aim to unravel underlying mechanisms of the development and progression of lung diseases, including asthma, COPD and pulmonary fibrosis. There will be a close collaboration with the consortium partners from the departments of Pulmonary Diseases and Thoracic Surgery of the UMCG (Prof. Dirk-Jan Slebos, Dr. Michiel Erasmus) and the departments of Developmental BioEngineering and Engineered Therapeutics of University Twente (Prof. Jeroen Leijten and Prof. Jai Prakash).
The UMCG has a preventive Hepatitis B policy. The UMCG can provide you with the vaccination, should it be required for your position.
We offer a 1 year postdoc position for 1 fte (36 hours), with the possibility to extend for 2 more years.
Your salary will be a maximum of €4,707. gross per month (scale 10), depending on your qualifications and relevant experience, based on a full-time appointment.
In addition, the UMCG will offer you 8% holiday pay, and 8.3% end-of-year bonus.
The conditions of employment comply with the Collective Labour Agreement for Medical Centres (CAO-UMC).
Please use the the digital application form at the bottom of this page - only these will be processed.
You can apply until 17 July 2022.
Within half an hour after sending the digital application form you will receive an email- confirmation with further information.