The aim of this thesis was to study phage infection in Streptomyces, focused on cell wall-deficient cells. Bacteriophages (or phages in short) attach to the cell wall of bacteria after which they replicate and lyse the host cell.

Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.

Atherosclerosis, in particular rupture of atherosclerotic plaques, is the underlying cause of most heart attacks or strokes and is the leading cause of death worldwide.

Atherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the vessel wall.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

Gaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes.

This thesis examines strategies to address the global threat of antimicrobial resistance (AMR). Antimicrobial resistance poses an increasing global health risk, highlighting the need for new treatments against Gram-negative pathogens.

In this research project, we aimed to obtain more insight in the role of mast cells in the immune driven disorders rheumatoid arthritis and atherosclerosis.

This thesis advances our understanding of lipid uptake, a vital first step in lipid metabolism, by developing innovative click chemistry-based tools to study how immune cells internalize lipids.

There is a need for alternative methods to replace, reduce and refine (3R) animal experimentation. Combining experimental data from high-throughput in vitro studies with in silico modeling is a promising approach to unravel the effect of chemicals on living cells and to gain a better understanding of…

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.

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

During embryonic growth, cells proliferate, differentiate, and collectively migrate to form different tissues at the right position and time in the body.

CONCLUSION: This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our observation that the induction of macrophage anti-tumor activity by L-MTP-PE required IFN-gamma may be of relevance for the optimization of L-MTP-PE therapy in…

The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease…

Bacteria have the ability to alter their morphology in order to adapt to changing environments.

Aspergillus niger is an important industrial producer of organic acids and enzymes producing large amounts of spent fungal biomass.

Promotoren: G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

The central question of this Vici proposal is to investigate if, and how actinobacteria exploit life without a cell wall.

This thesis focuses on two processes involved in fighting infections: metabolism and immune cell motility and navigation.

In this thesis, we have studied cell images from two types of cells, including pollen grains and the immune cells, neutrophils. These images are captured using a bright field microscope and a confocal microscope.

Influenza CD8(+) T-cell epitopes are conserved amongst influenza strains and can be recognized by influenza-specific cytotoxic T-cells (CTLs), which can rapidly clear infected cells. An influenza peptide vaccine that elicits these CTLs would therefore be an alternative to current influenza vaccines,…

Develop a prototype combined chemical-microbial enzymatical process for the sustainable, green recycling and revalorization of polyamides and polystyrene

In order to gain a better insight into the basis of the rapid jasmonic acid (JA)-mediated stress response, an integrated approach using a targeted high-resolution mass spectrometry-based (HRMS) platform, was conducted to monitor the metabolism of JA using the model system of cell suspension cultures…

Cell-based medicinal products (CBMPs) show great promise when it comes to the treatment of genetic disorders. However, there is limited knowledge about CBMP stability during their production, storage, and administration to patients. The main focus of my research is the characterization of CBMPs using…

A very large part of intravenously administered nanoparticles are cleared through the liver. Within the liver, most nanoparticles are thought to be sequestered by macrophages (Kupffer cells). To achieve effective cell-specific targeting of drugs and non-viral gene delivery vectors, improved mechanistic…

This thesis describes the development of a variety of mannosylated conjugates. Antigen presenting cells bear mannoside recognizing receptors that actively transport antigen into the cell. This thesis exploits this feature for the development of improved vaccines.

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells.

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained.

Promotor: J. Kuiper

Promotores: T.H.W. Bäck, A. Plaat, Co-promotor: F.J. Verbeek

In our research protein translocation from Agrobacterium into yeast and plant cells is studied to obtain fundamental insights in the translocation process

One of the major limitations in culturing complex tissues or organs is the lack of vascularization in the cultured tissue. Development of a functional capillary bed could overcome this problem.

This thesis aims to test in vitro pipelines to rapidly and cost-effectively identify molecular mechanisms that drive adverse outcomes in clinical use.

Promotor: Prof.dr. R. Verpoorte, Co-Promotores: N.R. Mustafa, A.E. Schulte

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

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…

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription.

Promotor: Prof.dr. R.M.H. Merks

This thesis describes the antimicrobial discovery strategy developed in our group, the den Hertog Group at the Hubrecht Institute. It includes a cultivation-based screening approach for novel antimicrobial agents from the source of fungi, and a bacterial time-lapse imaging approach for antimicrobial…

Light-Harvesting Complex II (LHCII) is responsible for light absorption and excitation energy transfer in plants and photosynthetic algae, while in high light it undergoes conformational changes by which it quenches excitations to prevent photodamage.

This thesis focused on the exploration of monolayer graphene as a membrane in direct methanol fuel cell (DMFC) applications, with improvements achieved through plasma exposure or damage- free chemical functionalization.

Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle.

Promotor: A.H. Meijer, Co-promotor: B.E. Snaar-Jagalska

The lipid matrix of the skin's stratum corneum plays a key role in the barrier function, which protects the body from desiccation. The lipids that make up this matrix consist of ceramides, cholesterol, and free fatty acids, and can form two coexisting crystalline lamellar phases: the long periodicity…

Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC.

The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the…

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects…

Multicellular giant algae Chara species have been widely used in physiological studies for decades.

Carbohydrates are present on the surface of bacteria making them suitable antigen candidates for vaccine development. This thesis deals with the synthesis of two carbohydrate-based components; the capsular polisaccharide of S. aureus type 5 and teichoic acids from staphilococci and enterococci speci…