Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

What are the functions of the endocannabinoid system?

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

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

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,…

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

The electrochemical oxygen reduction reaction (ORR) is an essential half-reaction for the utilization of hydrogen as a sustainable fuel, via the conversion of hydrogen to electrons and protons facilitated by the ORR. In the most common fuel cells, the ORR is requires high loadings of non-abundant platinum…

Activity-based protein profiling (ABPP) is a functional proteomics technique for directly monitoring the expression of active enzymes in cell extracts and living cells. The technique relies on irreversible inhibitors equipped with reactive groups (warheads) that covalently attach to the active site…

Promotores: Prof.dr. H. van Veen & Prof.dr. W. de Boer (Wageningen University)

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.

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 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.

Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.

Focus in skin research

Promotor: Prof.dr. G.P. van Wezel

Artificial photosynthesis aims to produce fuels from solar energy using chemical processes. In semi-artificial photosynthesis, a hybrid approach is taken using both chemical and biotechnology approaches. We aim to develop hybrid systems between light-harvesting nanoparticles and redox-enzymes (oxidoreductases)…

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

The goal of target discovery is to identify and validate proteins and biological pathways that are involved in the disease process. Modulating these target proteins and pathways with small molecules, therapeutic proteins or other biomolecules (e.g. mRNA) could deliver an effective and safe drug or v…

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.

Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.

Ceramides (CERs), cholesterol, and free fatty acids (FFAs) are the main lipid classes in human stratum corneum (SC, outermost skin layer), but no studies report on the detailed analysis of these classes in a single platform.

While bioinformatics methods deal with the analysis of sequence information (be it proteins or DNA), the field of cheminformatics is concerned with the analysis of small-molecule datasets.

To this day, all cyclophellitol-based inhibitors and ABPs have been close analogues of their natural substrate counterparts. As a result, these probes showed high selectivity towards their target glycosidases.

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…

Synthetic cells, also known as artificial cells or protocells, have wide ranging applications from drug delivery vectors to cell models. In biotechnology they can function as micro- or nanoreactors with possible applications in biocatalysis and photocatalysis. Phospholipids are by far the most commonly…

Why do plants produces always produced so many slightly differing metabolites within a particular chemical class?

Dr. at Max Planck Institute for chemical Ecology, Jena - Germany

BACKGROUND: Explant human skin equivalents (Ex-HSEs) can be generated by placing a 4mm skin biopsy onto a dermal equivalent. The keratinocytes migrate from the biopsy onto the dermal equivalent, differentiate and form the epidermis of 1(st) generation Ex-HSEs. This is especially suitable for the expansion…

Can Cyanobacteria be engineered to convert the greenhouse gas carbon dioxide into the valuable chemical isoprene?

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

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

Can bacteria be engineered to convert methanol into valuable chemicals with high efficiency?

Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…

Nanoparticles exhibit a number of adjustable properties, e.g., their size, shape, and surface and core chemistry, which can be further diversified with different functional moieties. This opens a broad field for application in diagnostic and therapy. In this respect, the use of a polymeric hybrid material,…

What is the most effective way to eliminate tumour cells? The DNA repair mechanism could play an important role in increasing the effectiveness of chemotherapy in the fight against cancerous cells. If we are to influence this mechanism, we need fundamental knowledge about how the mechanism works.

Artificial photosynthesis aims to produce fuels from solar energy using chemical processes. In semi-artificial photosynthesis, a hybrid approach is taken using both chemical and biotechnology components. We are developing hybrid systems, coupling light-harvesting nanoparticles to redox-enzymes (oxidoreductases)…

The Leiden Institute of Chemistry (LIC) is the basis for research and collaborations of the Leiden chemistry groups. Chemistry is the central science enabling a healthy future in a sustainable society. Chemistry researchers at Leiden University take a fundamental approach in finding tailored solutions…

Hermen Overkleeft and his colleagues Gideon Davies (University of York) and Carme Rovira (University of Barcelona) will receive a 9.1 million euros Synergy Grant from the European Research Council. Together, they will form the Carbocentre Synergy team for research into enzymes that work on glycans:…

Researchers at Leiden University have made a breakthrough in the study of the hereditary Pompe disease. Together with colleagues in York, they have developed a molecule that binds to the enzyme that is key to the progress of the disease. The findings have been published in ACS Central Science.

Alexander Kros studies supramolecular systems in a biological environment. The unifying theme between the projects in my lab is specific molecular recognition, i.e. the intermolecular interaction between complementary molecules with high affinity and selectivity. Studying, imitating and dissecting processes…

Dr. Erik Vijgenboom (IBL) and Dr. Peter Punt (IBL/TNO) obtained a new NWO-grant for their project FILAZYME to develop filamentous micro-organisms for enzyme production to degrade biomass.

Leiden chemists, together with colleagues at the University of York (UK) and Technion (Israel) have discovered a small, sugar-like molecule that maintains the integrity of tissue around a tumour during cancer. This molecule prevents tumour cells from spreading from the primary cancer site to colonise…

Target selectivity is an important aspect of any drug molecule, and certainly a parameter to be optimized. That is not trivial for a number of reasons. First of all hundreds of drug targets (receptors, enzymes, ion channels) exist, and no single lab in the world has assays for all of them.

A full overview of MCBIM PhD theses.

How do pathogenic mycobacteria alter lipid metabolism in human cells and patients, and which disrupted pathways could be targeted for new antibiotics?

best phd theses of the faculty of science Leiden - physics, chemistry, computer science, biopharmaceutical sciences, biology, industrial ecology, environmental sciences, astronomy, mathematics. thesis

Prof. Elizabeth de Lange is concerned with the allocation of resources for the conduct of science towards the goal of best serving the public interest. Also, while she underscores that there is still the need for using animals in drug research, she is concerned about this use, and advocates the use…