The research within the Division of Cell Systems and Drug Safety, headed by Prof. Bob van de Water, is focused on novel therapeutic modalities and novel concepts in early drug discovery, in order to develop more effective and safer therapeutic strategies. We generate advanced cell and computational…

Which brain cell does what, when Parkinson's disease arises? It won't be long before this jigsaw is solved piece by piece. Ahmed Mahfouz, computational biologist, combines bio-knowledge from Leiden with algorithms from Delft and is getting closer to finding the key.

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.

Source: Biosens Bioelectron, Volume 74, pp. 233-42 (2015)

Cardiovascular syndromes are the major cause of death in Western societies.

From molecule, to cell, to organism. The high-level drug research at the Cell Observatory aimes at reducing the spread of cancer and developing new medicines for tuberculosis.

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.

Treatment with special stem cells seems to be a good option for suppressing the immune system in organ transplants. Researchers are trying to learn from processes that take place in the human body during pregnancy.

Cell adhesion signaling

A new therapy for the serious Graft-versus-Host disease

This project investigates the influence that Arabic (esp. dialectal Arabic) has had on the Berber languages of Northern Africa.

Mechanobiology is a major area in biology, however, mechanics is currently a missing element in drug development pipelines. This has led to a high cost for the society. Mechanotoxicity of drugs often appears as a long-term side effect of drugs, and has led to removal of drugs from the market. Furthermore,…

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…

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…

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.

Promotores: Prof.dr. M.K. Richardson, Prof.dr. H.P. Spaink

How can we prevent drug-induced liver and kidney damage? PhD candidates Marije Niemeijer and Lukas Wijaya investigated what happens in the cells during the onset of this damage: a stress response. Both focused on a different subtopic and made some interesting discoveries.

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.

We have developed a microfluidic platform for complex 3D organotypic cell cultures (so-called organ-on-a-chip systems) which are suited for integration in 96 or higher well plate format.

Source: Br. J. Pharmacol., Volume 172, Issue 3, pp. 940-55 (2015)

The potential of bioneedles to deliver influenza vaccines was investigated.

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.

For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated…

Decision support tool for cell therapy commercialization and business development

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

We study cell-fate decision-making using embryonic stem cells as a model system. Stem cells integrate a large number of cues to direct their development into a great variety of cell types.

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

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…

During post-embryonic development into adults, animals face an environment that fluctuates constantly. For example, in nutrient availability, temperature, and osmolarity (e.g., salt concentration).

In this thesis, time-lapse fluorescent microscopy plays a pivotal role in investigating functional materials within living cells as well as the migratory behaviour of neural progenitor cells.

Regenerative medicine is a new way of treatment that helps impaired cells, tissues, and organs work well again. We do this by repairing, replacing, or restoring cells, tissues, and organs after damage from illness or injury. This includes treating long-term diseases such as diabetes, kidney diseases,…

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…

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

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.

This project investigates the role of art in the public and academic debate on biosolar energy

What is the most effective way to eliminate tumour cells? The DNA repair mechanism could play an important role in increasing the effectiveness of chemotherapy in the fight against cancerous cells. If we are to influence this mechanism, we need fundamental knowledge about how the mechanism works.

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,…

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.

We aim to unravel the molecular mechanisms involved in the transformation of eukaryotic cells by Agrobacterium.

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

Promotor: Huub J.M. de Groot, Co-promotor: Francesco Buda

The cellular metabolism of immune cells constitutes an important part of their proper function and activation. Using T cells as an example, this phenomenon is highlighted by the metabolic reprogramming that occurs in these cells upon activation.

We aim to engineer streptomycetes to fully exploit their potential for natural product productions, by a rational design and evolution approach.