Master student Research projects in Amsterdam UMC location AMC
Department of Medical Biology
In our department we provide MSc research projects of minimally 6 months. Students are supervised by dedicated scientists and participate in departmental scientific meetings and Journal clubs. A brief description of the available project is listed below:
1. Molecular mechanisms of endothelial barrier breakdown in the eye and brain
Brain edema, or swelling of the brain, is a potentially life-threatening condition, and diabetic macular edema (DME), swelling of the retina, is a major cause of blindness. Both disorders are the result of, respectively, loss of function of the neuroprotective blood-brain barrier (BBB) and the blood-retinal barrier (BRB) of blood vessels. We have found that inhibition of an endothelial cell-specific protein can prevent endothelial barrier breakdown in vitro and in vivo. In the current project, we would like to further explore through which mechanism this happens. Click here for more info.
Techniques: Endothelial cell culture, lentiviral transduction, confocal imaging, live cell imaging, electron microscopy, western blotting, qPCR.
2. Gene and (stem) cell therapy for cardiac rhythm regeneration
Cardiovascular disease is an increasingly common cause of death. In case of cardiac rhythm disease, an electronic pacemaker can be implanted. This ever more frequent procedure (300,000 a year in Europe alone) has severe limitations. Electronic pacemakers have limited battery life, and can break or become infected. In addition, electronic pacemakers do not adjust to increased demand for blood flow, e.g. during exercise or – in children – because of growth.
We are therefore looking into supporting patients with cardiac rhythm disease with a biological pacemaker. The Boink group wants to improve heart rhythm management by development of therapeutic viruses and (stem) cells as biological pacemakers. We have obtained in vivo proof-in-principle for therapeutic AAV (adeno-associated virus), and are now critically expanding our strategies for pre-clinical testing to include adenovirus and lentivirus, in several in vitro and in vivo models.
We provide Master student research projects of 6 or more months. Students become part of a dedicated team, and participate in ongoing research, including scientific meetings and conferences. More information about the research: https://www.medischebiologie.nl/boink-group/
Methods: DNA cloning and sequencing. Cardiac gene expression and knockdown (by RNAi, miRNA or lncRNA). Virus production and purification. Transfection and transduction of cell lines, stem cells, and primary cells. In vitro and in vivo cardiac models. Microsurgery. Microscopy, Western blot, Immune fluorescence and histochemistry, qRT-PCR.
Department of Public Health and Clinical Epidemiology, Biostatistics and Bioinformatics
In our department we provide a MSc research project of minimally 4 months (longer is preferred). A brief description of the available project is listed below:
1. To what extent are prenatal, postnatal and early childhood factors determinants of CIMT and intra-abdominal fat of 11-year-old children
Dr. Tanja Vrijkotte and Dr. Barbara Hutten
Cardiovascular diseases (CVDs) are the leading cause of death and remain one of the most important health challenges worldwide. Although most children are born with optimal cardiovascular health, clustering of cardiovascular risk factors already occurs early in life. Carotid intima media thickness (CIMT) is considered as a surrogate marker for CVD, which can already be measured in childhood. Increased intra-abdominal fat is a strong risk factor for metabolic diseases such as diabetes type 2. This project seeks to find early determinants (prenatal, postnatal and pre-school age) of increased CIMT as well as intra-abdominal fat and thereby provide knowledge for the development of effective strategies to optimize cardiovascular and metabolic health from the earliest age onwards.
Methods: Data for this study is available from the Amsterdam Born Children and their Development (ABCD)-study, a birth cohort study. This study was set up in 2003 to investigate the associations between early life conditions and children's development and health with specific interest for socioeconomic and ethnic disparities. Data collection concerning c-IMT and intra-abdominal fat measurements was part of the health measurements of Phase 4 of the ABCD-study. A random selection of 853 children were measured. Multivariable linear regression analysis with common epidemiological techniques for data analysis in SPSS will be used.
Student will help with ongoing data collection at age 15/16 (Phase 5), planned till the end of 2020. More information about the ABCD study: www.abcd-study.nl
Department of Anesthesiology
In our department we provide MSc research projects of minimally 6 months. Students are supervised by the PI and participate in departmental scientific meetings and Journal clubs. A brief description of the available projects is listed below:
1. Novel and optimal multimodal therapy against acute myocardial infarction
Acute myocardial infarction (AMI) remains one of the common causes of death and hospitalization worldwide. Improved treatment strategies for AMI are urgently needed for for the prevention of adverse cardiac remodeling and eventual heart failure. In this research line we explore several novel and high potential targets against acute infarction and combine
them to gain maximal reductions in infarct size in animal studies, with a keen eye towards applicability towards the clinical arena.
Techniques: isolated perfused mouse hearts, in vivo cardiac infarction model rat, stabile isotope for cardiac metabolism, cell death parameter analysis, western blotting, spectrophotometric enzyme analysis.
2. Unravelling the mechanisms of the effective diabetes medicine Empagliflozin
Dr. Coert Zuurbier and Dr. Nina Weber
The kidney-targeted Empagliflozin (EMPA) caused a large reduction in heart failure hospitalization and cardiovascular death in diabetes patients (Zinman B et al, NEJM 2015). Surprisingly, the underlying mechanisms are largely unknown. In this project we try to unravel the cellular mechanisms and actions of empagliflozin in the heart and endothelial cell.
Techniques: isolated perfused mouse hearts, isolated endothelial cells, stabile isotope for cardiac metabolism, genetic
manipulations of targeted genes, cell culture, cell physiology parameter analysis, western blotting, spectrophotometric enzyme analysis.
Department of Medical Biochemistry
In our department we provide MSc research projects of minimally 6 months. Students are supervised by dedicated scientists and participate in departmental scientific meetings and Journal clubs. A brief description of the available projects is listed below:
1. Aortic Aneurysms: how to predict them and how to inhibit further dilatation.
Aortic aneurysms are dilatations of the aorta, which result in prophylactic aortic surgery when the aneurysm grows beyond 5 cm in diameter. In Marfan Syndrome patients, aortic aneurysm growth and rupture is the main cause of mortality. It is difficult to predict which patient is at high risk of aneurysm development and rupture. We study aortic markers in human and Marfan mouse aortic tissue, to develop predictive tools for aneurysm growth and rupture. Moreover, we perform intervention studies in a Marfan mouse model to reveal new therapeutic approaches.
Techniques: cell culture vascular cells, histological analyses Marfan mice, mouse experiments treating Marfan mice.
2. Nuclear Receptor Nur77 reduces the inflammatory response of macrophages
The orphan nuclear receptor Nur77 (NR4A1) regulates a large variety of cellular processes and macrophage inflammatory signaling. We study Nur77-mediated gene regulation by comparing genome-wide DNA binding (ChIP-seq) and gene expression profiles (RNA-seq) in RAW264.7 macrophages. In this research project the bioinformatic analyses of databases provide novel clues on the role of Nur77 in macrophages, which will be explored in follow up experiments.
Techniques: bioinformatics, cell culture macrophages (mouse, human, cell lines), gain-of-function and knockdown experiments, RNA/protein expression, Seahorse metabolism assays.
3. Molecular regulation of lipid metabolism by LXRs and the ubiquitin proteasomal system
We are interested in elucidating the molecular mechanisms that govern cellular and whole-body lipid metabolism. Specifically, we focus on the role of the ubiquitin-proteasomal-system and of the nuclear receptors LXRs herein. We have identified several new genes that play a role in controlling sterol and fatty acid metabolism in cells and are using biochemical, cellular biological, and mouse models to investigate their function. In particular, we are aiming to understand the role of these genes in cardiovascular and metabolic disease.
Techniques: Culture of primary cells and cell lines, Genetic manipulation of cells and mice using CRISPR/Cas9- and transfection-based methodology, Molecular biology, Biochemical assays, functional genetic screens.
4. Immune cell interactions in atherosclerosis and obesity
We are interested in how immune cells talk to each other in cardiovascular disease and in obesity. We are particularly interested in one group of immune modulators: the immune checkpoint regulators. Using a combination of mouse models, cell culture models, FACS analysis, histology and western blotting, we are identifying pathways how immune checkpoint regulators and co-stimulatory molecules in particular drive atherosclerosis and obesity. Based on these pathways, we design and test small molecule inhibitors to treat atherosclerosis.
Techniques: Histology, Microscopy, Cell culture, Gene expression, FACS, Bioinformatics, Biochemicical and molecular assays.
5. Vascular Microenvironment and Integrity
We are interested in understanding how endothelial cells respond to mechanical changes induced by physiological dynamics taking place within the vessel wall. In particular we search for novel molecular events taking place at endothelial cell-cell junctions (VE-cadherin complex) and cell-extracellular matrix adhesions (integrin complexes). These are crucial structures that preserve vascular barrier function, and are tightly controlled during vascular development, angiogenesis and transendothelial migration of inflammatory cells. More information about the research: www.huveneerslab.eu
Techniques: Live fluorescence microscopy, endothelial cell culture, image analysis, shRNA-mediated knockdowns, biomechanical assays and biochemistry.
Department of Radiology
For duration and conditions of the project contact the principal Investigator.
1. Clinical implementation of state-of-the-art 4D flow MRI for cardiovascular diagnostics
4D flow MRI is an advanced non-invasive technique for visualization of blood flow. Clinical implementation of this technique is innovative and provides new insights into the function of heart valves, heart chambers and major blood vessels. This technique is particularly promising for the investigation of heart valve dysfunction.
This project focuses on the clinical implementation of 4D flow MRI. The candidate will specialize in 4D flow MRI (both scanning and post processing). With this knowledge and skills the candidate will conduct studies on the clinical value of 4D flow MRI in the context of mitral regurgitation.
Master student research projects department of Pathology, AMC
In our department we provide MSc research projects of minimally 5 months. Students are supervised by dedicated scientists and participate in departmental scientific meetings and Journal clubs. A brief description of the available project is listed below:
The Heart-Brain connection
In our research group we are interested in the connection between the heart and the brain. Despite the capacity of the brain to adapt cerebral blood flow to its own demand, systemic hemodynamic changes such as the function of heart, aorta and cerebral arteries may reflect on the cognitive functioning. In this project we study the molecular regulation of (extra- and intra-cranial) endothelial cells in protecting the brain against hemodynamic changes to understand their function in cardiovascular induced brain pathologies.
Techniques: We perform immunohistochemistry and imaging combined with quantitative molecular techniques.
Biomedical Engineering and Physics
For duration and conditions of the project contact the principal Investigator.
1. Development of a rat model for silent brain infarcts
Brain infarcts have overt and devastating consequences. However, small infarcts may occur much more frequently with aging and several cardiovascular diseases, and remain relatively unnoticed. We speculate that accumulation of small infarcts ultimately leads to cognitive impairment. In this project the student will help to develop a rat model for small infarcts by infusing microspheres into the cerebral circulation. Capillary perfusion is analyzed post mortem from brain sections. Potential recovery is studied by comparison of perfusion at day 1, day 7, and day 28 after microsphere infusion.
Techniques: Surgery, histology, 3D capillary analysis, immunohistochemistry.
2. End organ damage in hypertension, which treatment is most protective?
Chronic hypertension is known to cause damage to the brain, heart and kidney. Anti-hypertensive medication can lower blood pressure, but which type of drug is most protective in terms of end organ damage? In this study we treated hypertensive rats with either amlodipine (vasodilator) or atenolol (beta-blocker) until 1 year of age. Brain, heart and kidney were excised and stored. In this internship the student will asses end organ damage and compare tissues of normotensive rats, untreated hypertensive rats, and rats treated with amlodipine or atenolol.
Techniques: Sectioning, immunostaining, confocal microscopy.