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.

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

Bacteria have the ability to alter their morphology in order to adapt to changing environments.

In order to gain a better insight into the basis of the rapid jasmonic acid (JA)-mediated stress response, an integrated approach using a targeted high-resolution mass spectrometry-based (HRMS) platform, was conducted to monitor the metabolism of JA using the model system of cell suspension cultures…

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Evolution acts via mutations in amino acid sequences. Substitution of essential amino acids leads to a nonfunctional protein. l.

Naast de 2 TOP grants heeft het LIC ook nog 4 ECHO’s binnengehaald voor dr. Francesco Buda, professor Gijs van der Marel met Jeroen Codée, dr. Dmitri Filippov en professor Gilles van Wezel.

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.

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

Kieltyka

Promotors: Prof.dr. E. Bouwman, Prof.dr. E. Drent

This thesis describes the use of bioorthogonal proteins in immunological settings. It provides an introduction towards the field of protein modification, which was used throughout the thesis for the expression of proteins containing unnatural amino acids.

BlaC is the β-lactamase of Mycobacterium tuberculosis. We show that it can recover from inhibition by clavulanic acid and that phosphate helps it do so.

Promotor: A.P. IJzerman

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

The soil ecosystem consists of the largest reservoir of biodiversity on Earth.

The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.

Astronomical observations of cold regions in the universe show a rich inventory of ices. Part of these ices may end up on planets like our own, but in that journey they will be exposed to considerable amounts of radiation.

This dissertation focused on computational methods based on first principles calculations using the Density Functional Theory (DFT) framework. Emphasis was laid on affordable methods that can provide a tradeoff between computational expense and accuracy.

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

Dissolving microneedles are a subgroup of microneedle types that completely dissolve within the skin. During this dissolving process the vaccine, stored in the needle matrix, is released into the skin.

Promotor: Prof.dr. R. Verpoorte, Co-Promotores: N.R. Mustafa, A.E. Schulte

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

The research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In the field of atherosclerosis, we showed that the small peptide Lyp-1 can be used as a targeting molecule…

Synthesis and application of chemical biology tools to study immunomodulatory signaling lipids.

In this Ph.D. thesis, we characterized two novel upstream regulators of JUB1, HB40, and HB22, in Arabidopsis thaliana. In Chapter 2, we described functions of HB40 in modulating growth and development via the regulation of JUB1 and GA inactivation genes GA2OXs.

Promotor: Prof.dr. H.V.J. Linnartz, Co-Promotores: S. Ioppolo, H.M. Cuppen

As a contribution to the changing legislation and evolving societal attitudes concerning environmental issues, this project aims to enhance and manipulate the plants’ own natural defense mechanisms against western flower thrips (WFT).

Barrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function.

Pectin is a plant cell wall polysaccharide made of mainly D-galacturonic acid (GA) subunits. The potency of the filamentous fungus Aspergillus niger to naturally secrete high amounts of pectinases to degrade pectin has been utilized for the industrial production of pectinases.

Promotor: Prof.dr. J.G.E.M. Fraaije, Co-promotor: A. Kros

Aspergillus niger is an important industrial producer of organic acids and enzymes producing large amounts of spent fungal biomass.

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

The recently introduced nature-originated deep eutectic solvents, so-called natural deep eutectic solvents (NADES) are considered as truly green solvents, which composed of natural ingredients found abundantly in organisms.

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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.

Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

The focus throughout this thesis will be on gathering fundamental studies of the detailed structure and composition of the electrode/electrolyte interface effect on the rate and mechanism of key electrocatalytic reactions.

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.

Natural vanilla flavor is one of the most important in the world. However, the cost of this flavor is expensive. Production of this flavor by alternative methods, could reduce the cost.

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…

The thesis focuses on synthesis strategies in oligosaccharide campaigns, and the influence of protecting groups.

The aim of this thesis is to explore the use of Bioorthogonal Antigens to study the cross-presentation pathway.

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

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