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…

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.

It has been a long-standing mystery how complex biological structures emerge from such seemingly uncoordinated building blocks as cells and tissues, in the presence of only minimal environmental guidance.

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…

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…

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

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

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.

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.

Promotor: Prof.dr. B. van de Water

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

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…

Promotor: Prof.dr. M. Ubbink

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

Carbohydrates, alongside proteins and nucleic acids, constitute a crucial and versatile family of biomolecules present in all life forms. They manifest as monosaccharides, oligosaccharides, and polysaccharides, covalently bonded to proteins and fats. Carbohydrates are integral to plant and arthropod…

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.

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.

The expanding population and economic activity are driving up global energy consumption. Simultaneously, there is an urgent need to transition from fossil fuels to renewable sources to mitigate the climate crisis, primarily caused by fossil fuel combustion.

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.

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. M. Franx, Prof.dr. P.G. van Dokkum (Yale University)

Ons project Next444 richt zich op de toekomst van interdisciplinair onderzoek binnen de Universiteit Leiden.

Given the accelerating appearance of antimicrobial resistance, there is an urgent need for more fundamental research into novel antibiotic strategies. The work in this thesis helps to address this global problem by developing new antibiotic compounds, inspired by the antibacterial mechanisms of the…

How can prospective LCA be streamlined in a way that its practical application in research and technology development increases?

This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.

Co-ordination Action for Innovation in Life-Cycle Analysis for Sustainability: deepening, broadening and leaping forward the LCA methodology.

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

In this thesis new methodologies are developed for the detection and systematic study of radio sources in the early universe. This allows us to gain a deeper understanding of the formation and evolution of galaxies, the activity of supermassive black holes, and the final phase transition of our universe:…

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).

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.

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,…

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

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

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

Promotie

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

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

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

Promotor: S.M. Verduyn Lunel

Cathodic corrosion is a relatively unknown phenomenon that can severely etch metallic electrodes at cathodic (negative) potentials.

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.

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?

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

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

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.

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.

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

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

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