PhD Defence

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.

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

Almost all bacteria are enveloped by a cell wall that provides cellular protection.

Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo.

How are the epidermal lipid pathways involved in health and disease.

Can the pink-pigmented microbe Methylobacterium extorquens be genetically engineered to convert the sustainable raw material methanol into antibiotics?

Human and animal cells are very complex: very different chemical processes are going on at the same time, but they are separated from each other because the cells are divided in compartments. These compartments may also have a profound effect on the potential efficacy of therapeutics, because the drug…

Research at the BIOSYN group is comprised of the following research themes:

Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological…

LED3 is the combined effort of three excellent institutes of Leiden University. Through joined hands, we are able to give rise to a more effective early drug discovery pipeline. Let us briefly introduce the three institutes.

PhD Defence

Gubbens

Netherton Syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor. NTS patients have a profound impaired skin barrier function. Because SC lipids play a crucial role in the…

The company Azafaros was established in 2018 to translate innovative science from Leiden University and Amsterdam University Medical Center into novel disease-modifying treatment modalities for rare genetic metabolic disorders such as lysosomal storage diseases.

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)…

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

Microbial Sciences' contribution to the Bioactive Molecules research theme is to discover new bioactive molecules and enzymes and unravel their mechanisms of action, regulatory networks, and the (bio)synthetic pathways required for their production.

Using photosynthesis to generate energy, or using enzymes to effectively produce biofuel; Leiden chemists Huub de Groot en Hermen Overkleeft have both obtained an NWO TOP funding for their pioneering research. With the money they can take on new PhD students.

The work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate, and the second is the total synthesis of large fragments of the zwitterionic SP1 polysaccharide.

This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system.

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

In neonates and infants, body size, enzyme pathways, and expression and function of receptors and (target) proteins are still developing.

Promotor: Prof.dr. M. Ubbink

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

The work described in this Thesis is focused on the assembly of oligosaccharide fragments derived from a fungal polysaccharide, galactosaminogalactan (GAG) and fragments of the exopolysaccharide Pel, generated by Pseudomonas aeruginosa.

Supervisor: Xue Yang

Our focus is to optimize the fungal cell wall to both increase chitin production and chitin extractability.

Plants produce an astonishing variety of secondary metabolites (SMs) which are thought to play vital roles in the fitness of plants through ecological interactions.

Lecture

PhD Defence

PhD Defence

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.

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

Can new variants of daptomycin and the polymyxins be found?

Focus in skin research

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).

Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments.

Agrobacterium tumefaciens, a gram-negative plant pathogen belonging to the family Rhizobiaceae, is the causative agent of crown gall disease, which can affect many plant species including agronomically important ones.

Natural product inspired antibiotics to address resistance

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.

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.

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

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

Medical Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University. The section is headed by Prof. Dr. Hans Aerts.

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…

The filamentous bacteria Streptomyces are widespread inhabitants of terrestrial soils.

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

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.