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Barcoding atherosclerotic plaque cells: single cell sequencing to reveal heterogeneity and functional impact of atherosclerotic plaque cells

  • Full or part time
  • Application Deadline
    Thursday, July 16, 2020
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

A position for a PhD-student (gross €2325—€2972 per month) is available in dr. Sluimer’s team in the experimental vascular Pathology Dept. (http://www.pathologie.mumc.nl/medewerkers/sluimer). The team is embedded in the Cardiovascular Research Institute Maastricht (CARIM) of Maastricht University Medical Center and studies the role of hypoxia, inflammation and matrix turnover in atherosclerosis, and has strong links with Edinburgh University.

Atherosclerosis develops in the large arteries under the influence of high plasma cholesterol, hypertension and diabetes. Our group investigates the rupture of an atherosclerotic plaque, which is the actual cause of a myocardial infarct and / or stroke. We already know that this is partly due to a disturbed connective tissue production and degradation. In this project, supported by a prestigious Dutch VIDI grant, we will now investigate the underlying cause of this. The project will focus on mesenchymal cells, only recently detected in human and murine atherosclerosis. This intriguing cell exists in different subtypes, has great impact on matrix turnover, interacts with inflammatory cells and can stimulate the formation of new microscopic blood vessels (angiogenesis) in other pathologies, but its function and heterogeneity in atherosclerosis is unknown.
Here, we will use a very new technology to study the expression profiles of individual cells: single cell sequencing. Until recently, expression in whole pieces of tissue was studied, containing all kinds of different cells and subtypes, and it was impossible to determine the contribution of one cell type. This new technology offers the possibility to recognize new subtypes and study their function. The aim of the project is to detect new subtypes of mesenchymal cells in the vessel wall and to investigate whether they can repair the disturbed inflammation, and matrix turnover in plaques in order to prevent myocardial infarct and / or stroke in the future.

The experimental techniques involve basic research in cell culture models of cell death, genetic and pharmaceutical interventions in animal models of atherosclerosis with fluorescent reporters for markers expressed by new and established matrix-producing cells, and analysis of human plaque biopsies. Specific techniques include single cell sequencing, isolation of cell populations by flow assisted cell sorting, flow cytometry, single cell sequencing processing and bio-informatics (optional experience in R, or expression analysis), gene silencing, gene/protein expression analysis, immunohistochemistry and high content, automated (confocal) microscopy with fluorescent probes to analyse collagen production, cell death, proliferation, migration, inflammation, angiogenesis, lipid uptake, etc.

CARIM offers an outstanding scientific environment including shared core-facilities equipped with state-of-art instrumentation and knowledge, and an international reputation of excellence in research. The pathology lab consists of 20 international researchers involved in inflammation and atherosclerotic plaque stability. An extensive network of local, national and international collaborations is maintained with leading research groups, and international work visits are possible to stimulate the project quality.
Requirements
A degree in Biology, Health Sciences or Medicine with interest in cardiovascular research. Individuals with prior experience in cell culture and/or small animal models, and/or experience with bioinformatics (R, Seurat) are encouraged to apply. We value great team spirit, perseverance, a driven, independent and curious nature, international orientation, and excellent verbal and written communication skills in English.
Contract+ salary: fulltiem 4 years, gross €2325—€2972 per month
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 https://www.maastrichtuniversity.nl/support/um-employees

Funding Notes

funded by NWO, VIDI grant

Please addres application to dr. Sluimer, including a letter of motivation, CV, summary of study results, and any reference letters if available.

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