This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

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…

Promotor: S.M. Verduyn Lunel

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.

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…

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

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

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

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

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

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 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…

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

Promotor: Prof.dr. B. van de Water

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

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

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.

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

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.

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

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.

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

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

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

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.

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 development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes.

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…

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…

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…

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:…

Promotie

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

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.

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

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.

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

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

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

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?

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…

Promotie

Prof. Hermen Overkleeft is bekroond met de 2015 Jeremy Knowles Award van de Royal Society of Chemistry voor zijn innovatieve en inzichtelijke ontwikkeling van activity-based eiwit probes voor de beeldvorming en de identificatie van enzymen in gezondheid en ziekte. Van Overkleeft is in Leiden verbonden…

Description of Biotic ligand models: making an inventory of available models & assessment of the variability of the predicted HC5 using the BLMs in different Dutch water types (2005 - 2007)

Als mensen of dieren meerdere beslissingen achter elkaar moeten nemen herhalen ze vaak systematisch hun keuzes of wisselen deze af - zelfs als de keuzes die ze maken intrinsiek ongecorreleerd zijn. Dit gedragspatroon (ook bekend als 'sequentieel effect' of 'keuzehysterese') is al minstens een eeuw bekend…