Master student research projects in Amsterdam UMC location VUmc
Department of Physiology
1. Disease mechanisms in hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy is frequently caused by mutations in genes encoding sarcomere proteins. Our group defines pathomechanisms which are triggered by the sarcomere gene mutation, and studies which additional disease factors (gene variants, stressors) cause disease. We test specific compounds which may delay and/or reverse cardiac dysfunction and remodeling.
Techniques: protein analyses (electrophoresis, gel stainings, western blot), histological analyses/microscopy, functional studies (single cell, engineered heart tissue, endothelial cell-cardiomyocyte cross-talk).
2. Vascular integrity and endothelial cells
We study the molecular basis of vascular integrity. The research focus is on endothelial cells, the cells that line all blood vessels, and the machinery which controls their cell-cell contacts. This relates to control of cytoskeletal dynamics and protein degradation. Key proteins we are interested in are RhoGTPases and the enzymes that regulate their function. Our research combines biochemical and biophysical techniques with protein expression studies and high-resolution imaging of live endothelial cells.
Techniques: Endothelial cell isolation and culture; Western blotting; immunoprecipitation; cell transfection; siRNA studies; confocal microscopy; superresolution imaging; live cell imaging; expression of fluorescent proteins; biochemical assays for protein ubiquitylation; assays for endothelial integrity and vascular leakage; 2D and 3D flow models.
3. Long non-coding RNAs in cardiovascular disease
Most of the genome is transcribed in RNA, but only a fraction actually codes for protein. Our group studies the role of the so-called non-coding RNAs in cardiovascular biology. We particularly focus on long non-coding RNAs that are regulated during aging. We aim to unravel how individual non-coding RNAs regulate cardiovascular function, with the aim to identify non-coding RNAs that can be targeted therapeutically.
Techniques: Quantitative (real-time) PCR, RNA pulldown, RNA immunoprecipitation, cloning, deep sequencing analysis, advanced microscopy, siRNA transfection, gapmeR transfection, lentiviral overexpression, CRISPR-dCas9 overexpression tools.
4. Nuclear mechanotransduction in skeletal muscle adaptation and aging
Skeletal muscle has the remarkable ability to adapt to mechanical forces – when we do resistance training our muscles get bigger (hypertrophy), but when we age and reduce our activity, they get smaller (atrophy). Our lab is focused on understanding the cellular mechanisms that control this adaptation process, with a specific focus on the cell nucleus. Previously, it was thought that the nucleus was just a passive organelle, simply responsible for housing our genetic material (DNA). However, in recent years it has been shown that the nucleus can directly respond to mechanical forces, a process termed ‘nuclear mechanotransduction’. Our research integrates cell biology, bioengineering and whole-animal physiology approaches to study the role that nuclear mechanotransduction plays in skeletal muscle adaptation and aging.
Techniques: Myoblast and myofiber cell isolation and culture; confocal microscopy and live cell imaging; biophysical assays (micromanipulation, microfluidics); generation of engineered muscle tissues; western blotting; cell transfection; siRNA studies; histological analyses/microscopy; cloning
Applications accepted until Dec 1st 2020. Anticipated start date: mid-January to early February 2021.
Department of Molecular Cell Biology and Immunology
1. Targeting Immunometabolism to improve macrophage function and disease outcome
Our lab is interested in how metabolic pathways regulate macrophages. By targeting metabolic enzymes and pathways in macrophages, we aim to improve their functions and disease outcome, particularly focussing on cardiovascular diseases and cancers. To do so, we use a combination of human and mouse cellular and molecular models, in vivo approaches and validation in patient biopsies. We are especially interested in how immunometabolites control inflammation and regulate disease progression. By unravelling key questions in macrophage immunometabolism, our overall goal is to demonstrate whether and how targeting macrophage metabolism could be used for future therapy.
Techniques: metabolic profiling (including Seahorse flux analysis), functional screening, human and mouse primary cell culture, flow cytometry (FACS), bioinformatics
Department of Pathology
1. Viral myocarditis and sudden death
Viral myocarditis (VM) is an inflammatory disease of the heart that is associated with acute and chronic heart failure and also with sudden death and arrhythmias. Previous studies have shown that the myocardial inflammatory infiltrate associates with sudden death. In mouse models of VM as well as patient material we want to investigate how the local (heart) and systemic (blood, spleen and bone marrow) inflammatory responses associate with sudden death through cardiac arrhythmias and myocardial infarction.
Techniques: Echocardiography of heart function and ECG of conscious in VM mice; Tissue analysis via (immuno)histochemistry immunofluorescence, Tissue/cell culture, Flow cytometry.