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Adult cardiomyocytes are terminally differentiated cells, with a very low rate of proliferation in adult mammals. During normal wound healing after myocardial infarction, this low proliferation rate prevents regeneration of the lost cardiac tissue, shifting the balance towards a massive fibrotic response. Therefore, investigations aiming to redirect the wound healing process away from scar formation, into the direction of cardiac regeneration have high scientific and societal potential.
Previous research has shown that several signaling pathways, including WNT and TGF-beta signaling, are associated with reduced scar formation and induction of cardiac regeneration in zebrafish and new-born mice. However, inhibiting the fibrotic response is not without risk, as it may compromise the mechanical integrity of the infarct area and contribute to dilatation of the ventricles.
This PhD position is part of a recently funded ZonMW Open competition project entitled “The NEOHEART study: redirecting the wound healing after myocardial infarction towards cardiac regeneration by combining mechanical and pharmacological support”. This project is a collaboration between researchers from Leiden UMC, TU Eindhoven and Maastricht University, combining expertise in cell biology, biomaterials and pharmacology. The PhD student will benefit from this synergistic to be successful in completing this project.
The novelty of this project is that we will combine pharmacological stimulation of cardiac regeneration with mechanical support at the site of the infarct, to avoid dilatation of the ventricles or even rupture of the infarct area. To this end, we will develop a supramolecular fibrous mesh material that combines mechanical support of the infarct area with drug-eluting properties. This approach allows achieving pharmacologically relevant concentrations of drugs in the infarct area, without excessive systemic exposure that could cause side effects. The pharmacological and mechanical interventions will be tested in 3-dimensional co-cultures of cardiomyocytes and fibroblasts and on heart slices, before proof of concept is obtained in relevant animal models of MI. The PhD student located at UM will specifically focus on optimizing the 3-dimensional co-cultures and the testing of substances that promote the cycle of dedifferentiation, proliferation and redifferentiation required for regeneration.
Further details about the project can be found here: https://www.zonmw.nl/sites/zonmw/files/typo3-migrated-files/Gehonoreerde_projecten_Open_Competitie_ronde_2021_NL_en_EN.pdf
Are you excited to work in an international project team for an origination that is of societal significance? Are you self-motivated, curious and interested in research?
Do you have the skills required to become an excellent researcher in your field? Then a PhD position at CARIM might be the challenge you are looking for.
Candidates will be selected on the basis of the requirements outlined below. To be considered, candidates should make sure that their application demonstrates how they meet these requirements:
We are looking for a PhD-candidate with the following qualifications:
We offer a rewarding career at a young university in the heart of Europe, with a distinctly global perspective and a strong focus on innovative research and education.
We provide a stimulating, collaborative and interdisciplinary work environment with excellent opportunities for professional and personal development.
Maastricht University has an excellent international reputation, and Maastricht itself is a beautiful, open-minded city located in the center of Western Europe.
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 > About UM > Working at UM.
Maastricht University is renowned for its unique, innovative, problem-based learning system, which is characterized by a small-scale and student-oriented approach. Research at UM is characterized by a multidisciplinary and thematic approach, and is concentrated in research institutes and schools. Maastricht University has around 22,000 students and about 5,000 employees. Reflecting the university's strong international profile, a fair amount of both students and staff are from abroad. The university hosts 6 faculties: Faculty of Health, Medicine and Life Sciences, Faculty of Law, School of Business and Economics, Faculty of Science and Engineering, Faculty of Arts and Social Sciences, Faculty of Psychology and Neuroscience.
For more information, visit www.maastrichtuniversity.nl.
CARIM is one of the six schools of the Faculty of Health, Medicine and Life Sciences (FHML) of Maastricht University and is embedded within the Maastricht University Medical Center+ (Maastricht UMC+). CARIM collaborates closely with the Heart+Vascular Center of Maastricht UMC+. CARIM is one of the largest cardiovascular research institutes in Europe, producing more than 500 scientific articles and approximately 40 PhD dissertations per year.
Further information is available at the CARIM website: https://www.carimmaastricht.nl/
Department of Pharmacology & Toxicology
This project is situated within the Department of Pharmacology & Toxicology where a multidisciplinary team of biologists, chemists and toxicologists is working together to address mechanisms by which environmental chemicals and oxidative stress alter cellular processes to cause diseases and study the way in which intervention is possible. To reach these goals, the department's laboratory is well equipped with facilities for chemical analysis including mass spectrometry (MS) and electron spin resonance (ESR), the analysis of DNA damage and multiple state-of-the-art molecular biological techniques. The research is carried out on a (bio) chemical, cellular, tissue or whole organism level. The department consists of 16 staff members (4 professors, 3 senior lecturers and 9 lecturers/postdocs), 6 support technicians and 15 PhD students.
Maastricht University (UM)
Universiteitssingel 50, 6229 ER, Maastricht
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