The group of Dr. Roxanne Kieltyka designs and synthesizes molecules that self-assemble into polymeric materials using specific non-covalent interactions. These substrates can be used for numerous applications in medicine ranging from disease detection to cell delivery depending on the (bio)molecular…

This minor is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs. Students learn how disease and drug-induced alterations in signaling pathways can be used for the discovery of new drug targets and the development of personalized drugs.

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.

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

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…

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.

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…

Presents a novel philosophical account of psychedelic experiences, arguing that they can be induced by means other than psychedelics — such as meditation and yoga.

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…

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.

Methods of treatment for chronic illnesses are limited. Doctors and researchers at Leiden University Medical Center (LUMC) and Leiden University are working on new therapies as an alternative for organ transplants. The goal is to cure the illnesses by restoring organs to their original function. Stem…

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

Promotor: J. Kuiper

PhD defence

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…

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

Promotor: B. van de Water

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…

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.

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 focus of the described research in this thesis is on the oxidative stress response (Nrf2 pathway). The aim of the research presented in this thesis is to obtain more information concerning microRNAs which are involved in the Nrf2 pathway, to determine and evaluate the application of microRNAs for…

Advanced UHF MRI techniques provide powerful tools for studying the zebrafish brain, an emerging model in neurological research. In this work, various MRI and localized MRS methods are optimized and employed for UHF strength for studying the zebrafish brain.

Transcutaneous vagus nerve stimulation (tVNS) was tested in chronic worriers. tVNS may reduce spontaneously occurring negative thought intrusions. After a worry induction, there was no longer an effect of tVNS. tVNS did not affect physiological responding to worrying.

The RNA guided endonuclease based on the CRISPR/Cas system of Streptococcus pyogenus is a potent new tool for genome engineering in plants.

In a new study, we found that when we are exposed to potential harm to the other person, it improves our automatic attentional processes to avoid harm to that person.

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.

New technology offers many new possibilities for research, such as on dementia. ‘Organ-on-a-chip’ is a new technology in which small bits of organ are grown out of stem cells on a small plastic plate. A small piece of blood vessel, heart or nerve offers many new possibilities for research, such as…

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.

Cardiovascular diseases are the primary cause of death in the world with atherosclerosis as primary underlying cause.

The recognition that there may be more, so-called allosteric binding sites on a given receptor has also fueled our synthetic efforts. Over the last few years we have focused on many drug targets (adenosine A1, A2A and A3 receptors, the mGlu2 receptor and a classic ‘anti-target’, the hERG channel) to…

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…

An overview of awards and prizes granted to our staff and students in 2019, as well as special appointments and royal distinctions.

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.

Drug development is hampered by the limited predictive value of conventional 2D culture systems, which fail to recapitulate the complexity of the disease microenvironment and contribute to high clinical attrition rates.

The work done during this PhD research, aims to investigate the effect of tidal heatingin the observability of extra-solar satellites around exoplanets.

In this research group, headed by Bob Van de Water, cell signaling programs that underlie adverse drug reactions as well as cancer development and progression are unraveled. Adverse drug reactions involve cell injury in critical target organ cells which leads to the activation of cellular stress response…

Despite the fact that gold nanoparticles (GNPs) are one of the most studied nanoparticles, there is still a necessity for new approaches allowing for effective protective coating to enable wider use of GNPs in biomedical applications.

Reducing greenhouse gas emissions is one of the most pressing challenges that humanity faces in the coming decades.