A plasma is an ionized gas with very low electrical resistivity. As such, magnetic field lines are 'frozen in' and move with the fluid. Magnetic field lines that are linked, knotted and tangled, cannot be undone by the fluid motions.

In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.

To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies.

The intradermal administration route is attractive for vaccine delivery, because of the highly populated antigen-presenting cells in the skin. However, the skin’s main physical barrier, the stratum corneum, prevents vaccines from entering the skin.

Promotor: Prof.dr. E. Deprettere

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

In this thesis, the role of mast cells in atherosclerosis and novel therapeutic strategies to inhibit atherosclerosis progression are discussed. The first part of the thesis specifically focuses on the relation between mast cells and advanced human atherosclerotic plaque characteristics.

Promotor: P.J.J. Hooykaas, Co-Promotor: E.J. van der Zaal

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

Cardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood.

Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous…

Streptomyces present a valuable platform for natural product discovery. Lugdunomycin is a novel angucycline-derived polyketide from Streptomyces sp QL37, with unprecedented skeleton and antimicrobial activity.

This PhD-thesis presents a study on micron-sized particles, so-called colloids. By controlling the chemical and physical properties of these particles, such as the interparticle interaction and the particles’ shape, colloids can act as building blocks that self-assembly into larger structures.

Streptomyces bacteria are a valuable source of natural products, many of which are used in the clinic or in biotechnology.

Promotor: Prof.dr. J.P. Abrahams, Co-Promotor: N.S. Pannu

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

Antibiotic-resistant bacteria pose a major health threat. Addressing this challenge requires among others the development of new antibacterial compounds. The research described in this thesis focuses on discovering novel antibiotics from soil bacteria, specifically Streptomyces and Paenibacillus.Despite…

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.

The deeper understanding of an organism's pathology is important for developing treatments. Over centuries of systematic research, clinical researchers have demonstrated that the more information they acquire about the cellular properties and their organisation in the tissue, the better they can understand…

Promotor: A.P. IJzerman

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

Glucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger severe side effects and they induce acquired glucocorticoid resistance, especially during chronic systemic treatment…

Surface acoustic waves (SAWs) are mechanical waves that travel along the surface of a material and find many applications in modern technologies due to the ease of excitation on piezoelectric substrates via interdigital transducers (IDTs).

Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.

Promotie

Tuberculosis (TB) is associated with 1.5 million deaths annually. There is a need exists to optimize both current as well as novel antibiotic combination treatment strategies to improve the effectiveness and safety of treatments against TB.

Promotor: G.J.B. van Ommen

The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.

Glucocorticoids (GCs) are widely prescribed as anti-inflammatory drugs due to their well-established immunosuppressive effects.

Cryogenic electron microscopy (cryo-EM) is a powerful technique used to visualize the inside of cells and to study specific protein complexes. Within this thesis, I describe the use of various cryo-EM techniques to gain insight into the structural changes of the human pathogen, Vibrio cholerae, as it…

The formation of stars and planets happens over multiple scales, which can interact. In particular, planet formation happens in the dense, complex environment of star forming regions.

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

In this book liposomes are explored as delivery system for allergen-specific immunotherapy. Both cationic and anionic formulations are prepared with Bet v 1, one of the allergens in birch pollen.

Structural variants (SVs) are the hidden architecture of the human genome, and are critical for us to understand diseases, evolution, and so on.

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

Wat is er literair aan een grafische roman? Hoe verschilt de grafische roman van haar minder chique zusje, de strip? Welke vormen, genres en tradities kent de grafische roman? Wat is typerend voor de Nederlandse en Vlaamse grafische roman? In vier avonden reflecteren stripwetenschappers en -tekenaars…

Self-assembly offers a promising route to create complex structures and materials using simple building blocks. Through, colloidal self-assembly, we can understand the governing principles of the self-assembly process and unlock its potential in diverse applications in materials science, photonics and…

The research described in this thesis combines the latest insights in lysosomal function with lysosome centred cell signalling.

Endocannabinoids are lipid messengers that modulate various physiological functions by activating the cannabinoid CB1 and CB2 receptors. While the metabolism of endocannabinoids and their action at the CB receptors is fairly well studied, the molecular mechanisms governing their release and transport…

We showed that constitutive and inducible chemical and morphological defenses against Western flower thrips differ between tomato and chrysanthemum plants.

In this Thesis, novel charge induction mechanisms of ionic liquids are treated, tested and experimented on complex oxides, in particular cuprates.

Soil biodiversity is of great importance for the maintenance of multifunctionality in terrestrial ecosystems.

In this thesis, we consider various (electro)chemical phenomena at surfaces and nanoparticles and their underlying atomistic processes, which we studied using first-principles methods such as density functional theory.

This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system.

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.

In this thesis, two potential therapeutic targets for diabetic nephropathy were dentified and investigated. First, we show that glomerular clusterin is upregulated in diabetic nephropathy and demonstrated that recombinant clusterin protein can protect the podocytes against oxidative stress in vitro.…

Promotor: A.P.IJzerman Co-promotor: A. Bender

Promotor: Prof.dr. E.J.J. Groenen, Co-Promotor: M. Huber