The research described in this thesis combines the latest insights in lysosomal function with lysosome centred cell signalling.

The confinement of molecular catalysts in metal-organic frameworks has the potential to lead to significant improvements in selectivity, long term activity and catalyst stability.

In 2019 bestond de Universiteit Leiden 444 jaar. Deze bijzondere leeftijd vroeg om een bijzondere viering, samen met de inwoners van Leiden en Den Haag. In, met en voor de stad.

Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt

The progressive loss and degeneration of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). The onset and progression of PD can be triggered by multiple risk factors, for instance, genetic mutation, environmental exposure, and aging.

The plant hormone auxin regulates plant growth and development through polar cell-to-cell transport-generated maxima and minima. PIN FORMED (PIN) auxin efflux carriers determine the direction of this auxin flow through their asymmetric placement on the plasma membrane (PM).

In this dissertation, the synthesis and characterization of a series of iron complexes based on different ligand platforms are described.

Organic molecules in interstellar space are important as they influence the structure of galaxies and star formations. Studying catalytic processes in space allows us to understand how molecular species are formed and chemically evolved in the interstellar medium and solar system objects.

This thesis examines enzyme domain architecture and engineering to improve the breakdown of lignocellulose and starch, abundant biopolymers crucial for sustainable biofuel and biochemical production. Carbohydrate-active enzymes (CAZymes) facilitate this degradation, but the structural complexity of…

Sound is everywhere in the marine environment and hearing is therefore a very important for stimuli for fish. They use sound for orientation and communication, during migration, aggregation and spawning, but also for detection of prey and predators.

In this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models.

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

Kinase inhibitors are key therapeutic agents, particularly in oncology, yet their clinical efficacy is often hampered by off-target effects and limited understanding of their cellular target profiles.

Lysosomal storage disorders (LSDs) are a group of orphan diseases characterized by lysosomal dysfunction or impaired lysosomal catabolism and affect collectively about 1 in 5000 live births.

In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).

The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study.

In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.

S.S. Kolipaka’s thesis questions and investigates the survival prospects of reintroduced tigers and their offspring’s in the human dominated landscape of Panna tiger reserve in India.

Promotor: C.A.M.J.J. van den Hondel, Co-promotor: Sandra de Weert

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

Promotor: Prof.dr. H. J. A. Röttgering, Co-Promotor: M. Haverkorn

This thesis presents the first synthetic peptides ADP-ribosylated on serine, threonine, tyrosine, arginine and cysteine.

Op 20 oktober 2021 verdedigde Michael Ramsden het proefschrift 'The Role of the United Nations General Assembly in Advancing Accountability for Atrocity Crimes: Legal Powers and Effects'. Het promotieonderzoek is begeleid door promotor prof.dr. N.M. Blokker.

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.

The studies described in this thesis deal with glycosidases, in particular alpha-galactosidases.

Developing new medicines is one of modern science's most significant hurdles, a process marked by high costs, long timelines, and frequent failures of promising candidates.

Promotie

This thesis describes the synthesis, analysis of various tetrazine bearing compounds and use in bioorthogonal chemistry.

De Young Academy Leiden (YAL) is een selecte groep jonge academici aan de Universiteit Leiden. De YAL, opgericht in begin 2019, dient als platform om enthousiaste en ambitieuze jonge academici (post-PhD), die aan het begin van hun carrière staan, bij elkaar te brengen. YAL-leden vertegenwoordigen…

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

The research described in this Thesis was aimed at designing and synthesizing nature-inspired compounds as part of TB vaccine discovery.

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…

The goal of this thesis is to understand how interfacial parameters, such as the addition of organic additives, bulk pH or metal cations of the electrolyte, affect the relevant electrocatalytic reactions, i.e. electrochemical CO2 reduction reaction or hydrogen evolution reaction.

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.

Molecular complexes can be used as electrocatalysts for oxygen reduction, water oxidation, and/or hydrogen peroxide production.

Promotor: Prof.dr. M.T.M. Koper, Co-Promotor: F. Calle-Vallejo

CT scanning of skeletal remains can tell us about how strong or weak a persons bones were and we can relate that back to diet, activity, and reproductive factors.

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

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…

Promotor: Prof.dr. M. Ubbink

This thesis tackles the urgent challenge of antimicrobial resistance (AMR) through the design of novel antibacterial agents.

Hermen Overkleeft en zijn collega’s Gideon Davies (Universiteit van York) en Carme Rovira (Universiteit van Barcelona) ontvangen een ERC Synergy Grant ter waarde van 9,1 miljoen euro. Samen zullen zij het Carbocentre Synergy-team vormen voor onderzoek naar enzymen die werken op glycans: complexe koolhydraten.…

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

Cognitieve psychologie is de studie van mentale functies, waaronder aandacht, geheugen, bewustzijn, emotie, taal en actiecontrole. Het doel is om de complexe relaties tussen brein, cognitie en gedrag te begrijpen.

Promotor: S.M. Verduyn Lunel

Antibiotic-resistant bacteria pose a major health threat. Addressing this challenge requires among others the development of new antibacterial compounds. The research described in this thesis focuses on discovering novel antibiotics from soil bacteria, specifically Streptomyces and Paenibacillus.Despite…

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