Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases in the world, currently affecting 200 million people worldwide. It is characterized by a progressive loss of lung function with airflow obstruction that is not fully reversible. The key problem underlying COPD is defective airway and alveolar repair in response to inflammation and oxidative stress, causing bronchitis, small airways remodeling and emphysema. As current therapies do not modify the course of the disease in COPD, new therapies need to be developed.

The distal lung contains epithelial progenitor cells, which interact with structural cells such as fibroblasts to contribute to lung repair. This repair mechanism, which is driven by canonical WNT/β-catenin signaling, is impaired in COPD. Chronic inflammation and oxidative stress provide a hostile local microenvironment in the COPD lung, by causing damage, but also but also by hampering repair responses. The project aims to determine that the distortion of regenerative signaling is driven by a canonical to non-canonical WNT signaling switch, skewing signaling towards JNK, p38 and Rho-kinase, which lead to halted repair. These pathways provide rational drug targets for alveolar repair and we propose that it is possible to restore lung repair by targeting these pathways.

This consortium-based project is funded by the Dutch Lung Foundation and consists of a team of pharmacologists, pathologists, (stem) cell biologists and pulmonologists. In particular, experiments will be carried out to investigate i) how inflammation and oxidative stress promote a canonical to non-canonical WNT signalling switch; ii) whether this pathway cross-talk contributes to impaired lung repair in COPD; and iii) whether these pathways can be targeted pharmacologically in order to restore endogenous and progenitor cell mediated repair. This comprises a combination of technically challenging in vitro, ex vivo and animal studies, as well as the use of clinical samples.

As part of this consortium-based project, the PhD student will design and carry out theseexperiments and report the results in manuscripts and at scientific conferences.  Completion within 4 years is foreseen, with a PhD thesis defense at NUTRIM, Maastricht University.

This PhD Studentship for a 1.0 f.t.e. position for 1+3 (upon positive assessment) years is funded by the Dutch Lung Foundation and includes consumables costs. The candidate holds a MS degree in Biomedical, Molecular, Biological, Biochemical, Cell Biology, or equivalent (Bologna Declaration). The candidate is highly motivated, and has affinity with cell biology. As the project includes experiments to be carried out at partner locations in the Netherlands and in the U.S., flexibility is necessary. Personal skills include taking initiative and being a team player.

Dienstverband voor bepaalde tijd: 4 jaar.

Your salary would be € 2.222,- gross per month in the first year up to € 2.840,- gross per month in the fourth year according to the PhD-student salary scale.

Each year an evaluation will take place.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply.

For more information look at the website www.maastrichtuniversity.nl , Support/UM employees/Employment conditions.

Universiteit Maastricht

De Universiteit Maastricht (UM), is bekend om haar unieke, innovatieve, probleemgestuurde onderwijssysteem (PGO), dat wordt gekarakteriseerd door een kleinschalige en studentgeoriënteerde benadering. Het onderzoek aan de UM is multidisciplinair en thematisch van aard, en vindt geconcentreerd plaats in onderzoeksinstituten en schools. De UM heeft op dit moment zo'n 16.300 studenten en 4.300 medewerkers. Ten gevolge van het sterke internationale karakter is een groot deel van zowel studenten als medewerkers afkomstig uit het buitenland. De UM bestaat uit: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Humanities and Sciences, Faculty of Arts and Social Sciences en de Faculty of Psychology and Neuroscience.

http://www.maastrichtuniversity.nl/

NUTRIM School of Nutrition and Translational Research - Pulmonolgie

Het onderzoek vindt plaats binnen de vakgroep Pulmonologie (MUMC+). De groep is internationaal voorloper op het gebied van voeding en metabolisme bij longziekten.

Pulmonology is participating in NUTRIM School of Nutrition and Translational Research in Metabolism. NUTRIM initiates and catalyzes translational research into nutritional health benefits and risks focusing on metabolic and chronic inflammatory diseases. Through its research master and PhD programme NUTRIM aims to educate scientists of high academic excellence and ambassadors to support and develop the filed of nutrition, metabolism and toxicology within and outside the Netherlands. 16 Biomedical, clinical, and behavioural-science departments are incorporated within NUTRIM. The school is a partner in the national Top Institutes TI Food&Nutrition, TI-Pharma and the Centre for Translational Molecular Medicine (CTMM). These unique consortia of government, industry and research aim to stimulate the transfer of knowledge generated in fundamental research to Dutch industry and thus to strengthen its innovative power and competitive strength.

http://www.maastrichtuniversity.nl/nutrim