What are the host immune defence mechanisms that control intracellular infections and how are these subverted by pathogens?

How do mycobacteria subvert the defenses of host immune cells?

In this thesis, bioorthogonal chemistry is combined with correlative light-electron microscopy to selectively label and study pathogenic intracellular bacteria within the host immune cell.

Bead microrheology: Analysis of active and passive transport in living cells

Promotores: A.H. Meijer, H.P. Spaink

Promotor: Prof.dr. H.P. Spaink, Co-promotor: Prof.dr. A.H. Meijer

Supervisor: Natalia Ortiz Zacarías

Tuberculosis bacteria and other intracellular pathogens use cells of our immune system as Trojan horses to spread into tissues. Annemarie Meijer, professor of immunobiology, explains how research into innate defence mechanisms using zebrafish inspires novel strategies for infectious disease treatmen…

Cationic peptide amphiphile nanoparticles are employed for co-delivery of immune modulator CpG and antigen. This results in better targeting to the antigen presenting cells and eliciting strong Th1 response, which is effective against the intracellular pathogens.

The opportunistic bacterium Burkholderia cenocepacia is feared by cystic fibrosis patients and is emerging in hospital-acquired infections. An international study sheds new light on the infection mechanism of this opportunistic pathogen that may have large implications for treatment strategies.

Can effective synergists be identified to enhance the effect of antibiotics against Gram negative pathogens?

Natural product inspired antibiotics to address resistance

TRANSAUTOPHAGY is a European COST action to promote multidisciplinary research on autophagy and translation of knowledge to applications.

Human and animal cells are very complex: very different chemical processes are going on at the same time, but they are separated from each other because the cells are divided in compartments. These compartments may also have a profound effect on the potential efficacy of therapeutics, because the drug…

Source: Mol Psychiatry (2015)

Alexander Kros and co-workers describe how mesoporous silica nanoparticles (MSNs) are delivered into cells via membrane fusion thereby omitting endocytosis pathways. Fusion is induced by a pair of complementary coiled-coil lipopeptides inserted into the membrane of cells and in the bilayer of lipid-coated…

Can we enhance the capacity of host immune cells to kill mycobacteria via production of reactive nitrogen species?

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

Establishing human induced pluripotent stem cell (iPSC) CRISPR-Cas9-based fluorescent reporter cell lines for NF-kB signalling. We will use this to enable studying the dynamic activation and downstream signalling of Toll-like receptor and cytokine signalling in iPSC-derived differentiated cells in a…

How can zebrafish models be used to gain a better understanding of host-pathogen interaction mechanisms and to screen new drugs for infectious disease treatment?

PhD defence

On Monday 21 September Annemarie Meijer, Professor of Immunobiology, presented her inaugural lecture on immunobiology and infectious disease.

Animal Sciences’ contributions to the Host-Microbe Interactions research theme focus on the interaction of animal hosts with pathogenic microbes but also the beneficial role of the gut microbiome.

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

We perform multidisciplinary research at molecular, cellular, and organismal levels of animal biology to increase fundamental understanding of health and disease.

We perform multidisciplinary research at molecular, cellular, and organismal levels of animal biology to increase fundamental understanding of health and disease.

Who benefits from CXCR/CXCL chemokine signaling during infection: host or pathogen?

Michiel van der Vaart with a team from Leiden University and the LUMC, led by IBL-researcher Annemarie Meijer, discovered that DRAM1 is a protein that regulates anti-bacterial autophagy, a defense mechanism against infections such as tuberculosis.

The Chemical Probe Facility is part of the Leiden Early Drug Discovery & Development (LED3) center. Activity-based protein profiling (ABPP) is one of the pillars of chemical biology. ABPP determines the activity of entire protein families in living cells and tissues under physiological conditions, such…

Annemarie Meijer is appointed full Professor of Immunobiology. Meijer’s research focuses on immunobiology and infectious disease. She uses the zebrafish as a model for understanding mechanisms of host immune defense against intracellular bacterial pathogens.

How do plants lure microscopically small 'support teams' into their roots for protection against diseases? And what functions are activated in the microbes and the plants?

This thesis explores different avenues to develop insurmountable antagonists for CC Chemokine Receptors, such as CCR1, CCR2 and CCR5.

The goal of hit and lead optimization is to optimize suitable chemical starting points that can modulate a drug target. The methods and technologies used are similar to those in Hit Discovery, but once the compound has shown activity in an animal model, it moves from 'hit' to 'lead.'

Vancomycin is a last-resort antibiotic for the treatment of many Gram-positive bacterial infections, while remaining inactive against Gram-negative strains.

Cryogenic electron microscopy (cryo-EM) is a powerful technique used to visualize the inside of cells and to study specific protein complexes. Within this thesis, I describe the use of various cryo-EM techniques to gain insight into the structural changes of the human pathogen, Vibrio cholerae, as it…

How can Staphylococcus aureus bacteria subvert the host immune system?

The bacterium Vibrio cholerae is a serious threat to our health because it is the causative agent of cholera. Worldwide, over a billion people per year are at risk of cholera infection. New strains of V. cholerae are resistant to the multiple drugs used to treat cholera, meaning that new types of drugs…

Fungi germinating in the lungs of patients. Doesn’t sound too nice, does it? Luckily, humans can deal with this normally, and we are able to clear the infection before anything comes to harm. However, in people with health issues, Aspergillosis can cause a lot of damage, especially if the fungus becomes…

PhD defence

Mathematical and computational analysis of the dynamics of polar transport of the plant hormone auxin.

Autopaghy is an intracellular degradation system which targets cytosolic components to lytic compartments for degradation and recycling of the building blocks of the cell.

Currently, several successful vaccines are available. However, for pathogens with a highly variable genetic composition, and for which serum IgG antibodies are not a useful correlate of protection, effective vaccines are yet to be developed.

Promotores: Prof.dr. C.A.M.J.J. van den Hondel, Prof.dr. V. Meyer (Technische Universität Berlin)

The word ¨pyroptosis¨ can be understood as ¨fiery falling¨, which describes the bursting of pro-inflammatory signals from the dying cell. Our observations indicate that pyroptosis also ¨spreads like wildfire¨ and once a cell dies via pyroptotic cell death, neighbouring cells are more prone to die as…

Promotor: Prof.dr. J. Memelink