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…

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…

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

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…

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

Promotor: A. Doelman, Co-promotores: P.J.A. van Heijster; A. Zagaris

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

Promotor: J. Kuiper

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.

The loss of T-cell homeostasis and tolerance towards self-antigens is the underlying cause of autoimmune and inflammatory diseases like atherosclerosis, rheumatoid arthritis or type I diabetes. Traditionally, the treatment of these diseases consisted on systemic immune suppression, which can entail…

Chemist Roxanne Kieltyka has received an ERC Starting Grant of 2 million euros. In her lab, she creates gels that mimic the instructive material that supports cells in our body. With the grant, she aims to make these gels stiff and tough, and to create a bio-printed miniature heart ventricle.

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.

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

Promotores: Prof.dr. H.J.M. de Groot, Prof.dr. J. Matysik (Universitaet Leipzig)

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

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…

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.

Sara Polak, PhD researcher and lecturer at LUCAS, has won a Fulbright scholarship to work on her research on Franklin D. Roosevelt at Yale University from September 2014 till February 2015.

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…

Dr Sara Brandellero, Assistant Professor in Brazilian Studies (LUCAS), was invited by the State University of São Paulo (UNESP/Araraquara) and the Federal University of São Carlos (UFSCAR) as visiting professor for the week of 8-12 June 2015.

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.

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…

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

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…

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…

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

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…