This work describes the use of click-to-release chemistry to get spatiotemporal control over immunocytokine activity. Until now, immunocytokines (cytokines coupled to a tumor-targeting-moiety) remained active throughout the body, being able to bind their respective receptors, causing mild to severe…

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

Glucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger severe side effects and they induce acquired glucocorticoid resistance, especially during chronic systemic treatment…

Promotores: G.W. Canters, T.J. Aartsma

The research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study. Enzymes inherently embody a delicate balance between activity and stability, and the acquisition of new enzymatic…

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

Promotor: J.A. van Veen, Co-promotor: E.E. Kuramae

Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.

The key characteristic of active matter is the motion of an emergent collection (such as a flock of birds), which is driven by the consumption of energy by its active components (i.e. individual birds).

Promotor: G.P. van Wezel, Co-Promotor: E. Vijgenboom

Organisms often need to adapt more efficiently and devise new strategies for surviving difficult ecological circumstances.

In most applications, electrocatalysts exhibit a large surface area to volume ratio, for example using nanoparticles.

The role of the interfacial environment during electrochemical reactions has been increasingly valued, especially for those reactions involving protons or hydroxyl ions.

Promotor: Prof.dr. B. van de Water

Due to their central physiological roles in living organisms, retaining beta-glycosidases have been the subject of tremendous research efforts to examine their structure/function relation using numerous biophysical and biochemical approaches.

Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide,…

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

Novel entities may pose risks to humans and the environment. The small particle size and relatively large surface area of micro- and nanoparticles (MNPs) make them capable of adsorbing other novel entities, leading to the formation of aggregated contamination.

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.

This thesis describes the design and development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes.

Promotores: Prof.dr. G.W. Canters, Prof.dr. T.J. Aartsma

Outflows are crucially important for the gas budget and evolution of luminous star-forming galaxies and AGNs, with observed mass outflow rates of the same order as the star formation rate. Greater star formation and black hole growth lead to more intense feedback and outflows, resulting in self-regulated…

In this dissertation iron-based homogeneous catalysts were synthesized, characterized and investigated for water oxidation activity.

Electrocatalysis allows for storing electricity or converting it into chemical bonds, producing chemical building blocks and fuels using renewable resources.

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…

Cardiovascular diseases (CVDs) are the leading global cause of mortality. Endothelial dysfunction, an early reversible stage of CVD development, is marked by decreased nitric oxide production linked to Ca2+ influx in endothelial cells.

Marine sponges are important members of reef ecosystems, as they play ecological roles that are essential for the health of the reef.

Promotor: M.T.M. Koper, Co-promotor: J.B.F. Juurlink

Metals surfaces form a group of effective catalysts for the reaction of small molecules such as hydrogen (H2).

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Streptomyces are prolific producers of enzymes and secondary metabolites, including more than 50% of all clinical antibiotics. This makes them highly attractive for medical, biotechnological, and industrial purposes.

Streptomyces present a valuable platform for natural product discovery. Lugdunomycin is a novel angucycline-derived polyketide from Streptomyces sp QL37, with unprecedented skeleton and antimicrobial activity.

Salicylic acid (SA) is a plant hormone, which is involved in the defense responses to pathogens and to abiotic stress, and in the regulation of plant growth and development.

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.

This thesis investigates catalytic reactions at the atomic scale using scanning tunneling microscopy (STM), with a focus on Fischer–Tropsch synthesis, a key industrial process that converts hydrogen and carbon monoxide into liquid fuels.

Lipid nanoparticles (LNPs) have enabled the success of mRNA vaccines but remain limited in broader therapeutic use by challenges in delivery efficiency, targeting, and mechanistic understanding.

Lezing

Een nieuwe techniek, die gebruikt maakt van fluorescente beeldvorming om het gedrag van enzymen te volgen, kan de medicijnontwikkeling voor kanker, ontsteking en nierziekte bevorderen. Onderzoekers van de Universiteit van York en Universiteit Leiden hebben deze bevindingen in Nature Chemical Biology…

Promotor: Huub J.M. de Groot, Co-promotor: Francesco Buda

Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink Co-promotor: Dr. B.E. Snaar-Jagalska

Promotors: Prof.dr. G.R. de Snoo, Prof.dr. G.A. Persoon, Prof.dr.ir. H.H. de Iongh

Promotores: H.S. Overkleeft; G.A. van der Marel Co-Promotor: B.I. Florea

Hydrogen peroxide (H2O2) is an important bulk chemical that is used in various industrial processes. More than 95% of the H2O2 used in industry is made via the anthraquinone process during which a large amount of energy is going to waste.

This thesis investigates how galaxies form and what diversifies the evolutionary histories of galaxies.

Nanodiscs are small, disc-shaped structures designed to mimic biological cell membranes, composed of a lipid bilayer stabilized by scaffold proteins. Membrane proteins play crucial roles in essential processes such as nutrient and waste transport, molecular recognition, and cell signalling, making them…

Soil is a home for an unbelievable diversity and abundance of microbial life that is essential for supporting life on our planet.

Promotie