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

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

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: 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…

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…

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.

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…

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…

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…

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.

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…

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…

PhD defence

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…

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

Immunotherapies for cancer are an emerging class of therapeutic strategies which aim to treat cancer via augmentation of the immune system.

This thesis describes how complex and real-world relevant analytical solutions can be found starting from a simple Nagumo problem posed on one or two-dimensional lattices.

Embryonic stem cells have the remarkable ability to develop into any type of cell. On their way to become for example a liver or a heart cell, they must repeatedly decide between alternative developmental paths. How they make these decisions is largely unknown. An international team of biophysicists…

Source: Mediators Inflamm (2014)

The Leiden University Medical Center (LUMC), the Danstem Institute from the University of Copenhagen and the Murdoch Children’s Research Institute in Melbourne have received 300m euros from the Novo Nordisk foundation. The aim of this new international consortium is to bring stem-cell based therapies…

Kidney failure is a serious issue because kidneys cannot regenerate themselves after injury. A possible solution consists of artificially growing healthy kidney tissue. To achieve that, scientists first need to understand kidney development during the earliest stages, in the fetus. Leiden researchers…

A new mathematical model may explain how body cells get their shapes and what makes them move within a tissue. The model provides fundamental knowledge for applications in tissue engineering, amongst other things. Publication in open-access journal iScience.

Zebrafish-human communication shows that cancer cells lacking a signaling protein are less able to develop aggressive metastatic properties. This discovery has been made by molecular cell biologist Claudia Tulotta. PhD defence 14 June.

Prison staff are working under high pressure. The current proposal for cell sharing is the final straw. Associate Professor Esther van Ginneken appeared on Dutch news programme ‘Nieuwsuur’: ‘Serious incidents have occurred, including the murder of a cellmate.’

More allowance should be made for differences between municipalities, argues Geerten Boogaard, Thorbecke Professor of Local Government. The Municipalities Act could, for instance, offer a ‘menu of options’ for the decision on whether to have an elected mayor. Professor Boogaard will deliver his inaugural…

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases.

Viral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge…

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.

Promotor: Prof.dr. T. Schmidt

Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by various epidermal alterations. Filaggrin (FLG) mutations are a major predisposing factor for AD and much research has been focused on the FLG protein.

Cardiovascular diseases are a leading cause of death worldwide, and better models are urgently needed for disease progression studies and drug development.

Biophysicist Rolf Harkes has developed a microscope to optically localize individual molecules in living cells. It improves monitoring of diseases like cancer and Parkinson’s at the cellular level. Defende PhD thesis on t13 January 2016.

In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique.

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…

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

The overall theme of this thesis is to complement the electrochemical data acquired in fuel cell research with in situ X-ray photoelectron spectroscopy (XPS) and soft X-ray absorption spectroscopy (XAS).