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…

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

Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel

Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel

In this thesis, the discovery and optimization is described of chemical tools to study the N-acylethanolamine (NAE) biosynthetic pathway.

Promotor: Prof.dr. B. van de Water, Co-promotor: L.S. Price

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…

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…

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

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…

In the research programme Microbial Sciences we perform state-of-the-art research in the field of biotechnology and microbial sciences.

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

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.

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.

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.

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.

Sphingolipids are important membrane compounds with a variety of functions. In mammalian cells, different enzymes are involved in the metabolism of sphingolipids, but interruption of this metabolism process leads to different diseases.

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.

The research in the Biosyn group is focused on the design, synthesis and function of the four major types of biomolecules: nucleic acids, carbohydrates, peptides and lipids and hybrid structures thereof. These biomolecules and their derivatives are used in drug discovery and chemical biology, to develop…

Supervisor: Xue Yang

PhD defence

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

N-acylethanolamines (NAEs), including N-arachidonoylethanolamine (anandamide, AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), are signaling lipids that play an important role in different physiological process.

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

Promotor: Prof.dr. M. Ubbink

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.

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.

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

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.

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

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 main research theme in the group of Dennis Hetterscheid is to understand and mimic bioinorganic multi-electron processes that are relevant to our future energy infrastructure. Reduction of protons generates hydrogen that can be used as a chemical fuel. Alternatively to gaseous hydrogen, the reduction…

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).

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

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.

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…

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

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.

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,…

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.

The filamentous bacteria Streptomyces are widespread inhabitants of terrestrial soils.

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

Focus in skin research

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.