The aim of this thesis is to study cell-cell interactions and the development of an assay to explore and quantify the exchange of membrane compounds.

Despite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we probably only know a subset.

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.

In this thesis, we describe the potential of cell mechanical phenotyping for immune cell characterization, diagnosis, drug testing, as well as treatment of disease.

Mechanical interactions between cells and their environment play an important role in many biological processes.

Promotor: Prof.dr. J. Kuiper

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.

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

Cell-based medicinal products (CBMPs), such as CAR T cells, are highly complex biopharmaceutical products offering various treatment options for serious illnesses such as cancer or autoimmune diseases.

Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.

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.

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…

This work describes the use of click-to-release chemistry to get spatiotemporal control over immunocytokine activity. Until now, immunocytokines (cytokines coupled to a tumor-targeting-moiety) remained active throughout the body, being able to bind their respective receptors, causing mild to severe…

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.

In this thesis, single-cell approaches were applied to characterize the impact of aging on the immunological B cell landscape in different models of atherosclerotic cardiovascular disease, with the goal to identify and study new B cell-associated biomarkers and therapeutic targets to halt atherosclerosis…

A new type of tripodal squaramide-based supramolecular hydrogels is developed and studied.

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

Almost all bacteria are enveloped by a cell wall that provides cellular protection.

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

This dissertation aims to advance understanding of amoeboid single cell migration under the influence of changing physicochemical environmental properties. The particular focus is on the relatively unknown influence of differing physical properties in the extracellular environment, such as the migratory…

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Acute cardiovascular syndromes, including myocardial infarction or stroke, are the principal cause of death in the Western society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in…

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.

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.

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

There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.

The bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and hyperosmotic conditions, can induce bacteria to shift to a wall-deficient state. It is unknown whether the lack of…

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…

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 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…

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

Promotores: Prof.dr. G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Promotores: Prof.dr. E.A.L. Biessen, Prof.dr. T.J.C. van Berkel

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

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

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

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

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 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…

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…

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…

The way organisms develop from the initial single-cellular state to a complex final assembly like the human body, and how the final body is maintained throughout life, is one of the greatest mysteries and it’s understanding one of the biggest scientific challenges.

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

Promotor: Prof.dr. H.P. Spaink, Co-promotor: Dr. B.E. Snaar

Promotor: Johan Kuiper, Co-promotor: Saskia C.A. de Jager

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