The relative simplicity of the bacterial cell, short generation times and well defined and inexpensive culturing conditions have significantly contributed to our understanding of many complex biological systems. Yet the workings of the bacterial genome, seemingly impossibly compressed within a tiny…

Promotores: Prof.dr. H. van Veen & Prof.dr. W. de Boer (Wageningen University)

Authoritative and cutting-edge, Bacterial Chromatin: Methods and Protocols aims to be useful as an up-to-date reference work for scholars in the bacterial chromatin field, those entering the field from adjacent research fields, and scientists in the eukaryotic chromatin field.

This work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third-generation ring-closing tandem metathesis (RCM) linker to better exploit the potential of automated synthesis.

The main focus of the thesis is the discovery and development of novel inhibitors of bacterial metallo-β-lactamases (MBLs).

Mechanical forces are known to play an important role in bacterial colonies. In this dissertation, we study the self-organization at various stages of growing bacterial colonies, and focus on the mechanical effects of cell growth.

Bacterial chemosensory arrays are protein assemblies that are the key structural and functional component for motile bacteria to sense their internal or environmental chemical signals.

Autophagy is a fundamental degradative process, maintaining cellular homeostasis and functions in host defense against intracellular pathogens, including mycobacteria and Salmonella.

Bacteria often experience external challenges, such as changes in environmental conditions or attacks by bacteriophages.

Promotores: J.A.van Veen, P.L.G.Klinkhamer. Co-promotor: E.E.Kuramae

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 describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.

Agrobacterium tumefaciens, a gram-negative plant pathogen belonging to the family Rhizobiaceae, is the causative agent of crown gall disease, which can affect many plant species including agronomically important ones.

Promotor: G.A. van der Marel, Co-promotor: J.D.C. Codée

An international team with researchers from Leiden revealed how a bacterium repurposed an internal system to control its movements. Movement control is very important in host invasion, which can lead to disease. Publication on 27 April in Nature Communications.

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…

Mapping of bacterial genomes to combat infectious diseases

Can we determine the 3D structure of a chemotaxis core complex using single-particle reconstructions via cryo-EM?

Bacterial biocatalysis constitutes a sustainable alternative for high-value chemicals production by enabling the utilization of renewable feedstocks.

What are the genes and molecular mechanisms involved in bacteria-mediated plant drought tolerance?

In order to gain insight into the structure and function of the molecular complexes involved in chemotaxis, we use electron cryotomography (ECT). This technique allows us to directly study microbes in their native state at resolutions capable of visualizing individual proteins.

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The structure of bacterial cells provides crucial clues about their interaction with their host. What are the key structural features of a bacterial cell that determine pathogenicity? What roles do these structures play in the life cycle, and how do they change during the infection process?

Microbial Sciences' contribution to the Evolution & Biodiversity research theme focuses on understanding how bacteria sense and respond to their environment, and how bacterial diversity and evolution is influenced by cooperative and antagonistic interactions taking place between microbes.

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

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

1. To what extent do metallic NPs added to soil extractions change the activity, abundance, or community composition of microbes? 2. How do the effects of metallic NPs on soil microbes differ from the effects of the ions shedding from corresponding NPs?

What are the principles of genome folding and dynamics in bacteria?

The Quantitative Pharmacology group headed by Coen van Hasselt focusses on the application of state-of-the-art quantitative pharmacometrics and systems pharmacology modeling combined with translational experimental models to develop personalized treatment strategies for antibiotics and to combat antimicrobial…

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

The rapidly increasing commercial application of metallic nanoparticles within products will inevitably enhance the amount of NPs being released into soil.

Promotor: H.P. Spaink, A.H. Meijer Co-promotor: R. Marin-Juez

The overall objectives of my thesis are to investigate the dynamics of the sorghum root microbiome and to explore the beneficial effects of the root microbiome on sorghum growth and stress tolerance.

Natural product inspired antibiotics to address resistance

Plant-microbe interaction resulted in different physio/chemical responses by host plant and interacting rhizobacteria.

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

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.

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.

Nucleoid associated proteins maintain the architecture of the bacterial chromosome and regulate gene expression, hinting that their role as transcription factors may involve local three-dimensional chromosome re-modelling.

The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.

Bacteriophages, or phages for short, are the most abundant biological entity in nature. They shape bacterial communities and are a major driving force in bacterial evolution.

The European Lead Factory has been created with the ultimate goal to develop lead drug candidates to address neglected diseases including bacterial infections, psychiatric disorders and oncology.

PhD defence

An overview of Quantitative Pharmacology projects

Gubbens

The bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and hyperosmotic conditions, can induce bacteria to shift to a wall-deficient state. It is unknown whether the lack of…

The overall aim of this project is to understand, on the molecular level, how the bacterium V. fischeri cells interacts with their squid host.