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

Transplantation of labial salivary glands to the eyelids for patients with dry eye appears to give excellent results clinically.

Can a new proteomics workflow be developed to link genes and gene clusters to bioactive molecules, identify novel compounds and enhance the production in the Streptomyces lividans enzyme?

The chemical synthesis of inhibitors and probes targeting endo-glycosidases.

The power of personalized nutrition lies in being able to conduct clinical research on healthy people while capturing metabolic markers sensitive to the impact of environmental and metabolic stressors (e.g. diet, changing sex hormones and the menstrual cycle).

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

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

PhD Defence

PhD Defence

The current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced humoral responses have not yet been characterized in detail.

PhD Defence

Actinobacteria are Gram-positive bacteria that have a complex multicellular life cycle and are well known for their ability to produce a wide range of bioactive natural products (NPs).

While there are numerous and extremely advanced methods to sequence the genome, only a few methods exist to sequence the proteome. The Vidi project of Grégory Schneider promises to shed light on the most difficult paradigm of proteomics: achieving an error-free determination of the sequence of single…

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

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 human body consists of hundreds, perhaps thousands of different types of cells, each with different morphologies and functions, despite having the same genome.

Pathways of toxicity

Towards a Biological Understanding of the Middle to Upper Palaeolithic Transition

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…

PhD Defence

PhD Defence

PhD Defence

Diacylglycerol lipase (DAGL)-α and -β are enzymes responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Selective and reversible inhibitors are required to study the function of DAGLs in neuronal cells in an acute and temporal fashion, but they are currently lacking.…

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…

Promotor: H.S. Overkleeft, Co-promotor: B.I. Florea

In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.

Dr. in Biomedical NMR spectroscopy, LUMC, Leiden - The Netherlands

A model method: A strategy that combines a knowledge-based in silico design approach and the development of novel activity-based probes (ABPs) for the detection of endogenous diacylglycerol lipase-α (DAGL-α) is presented. This approach resulted in the rapid identification of new DAGL-α inhibitors with…

The CIGR brings together a diverse range of unique expertise in genome research rooted in biology, chemistry and physics. Members of the CIGR investigate genome folding and genome transactions. An important aspect is direct as well as long term relevance for medicine. The available expertise extends…

The CMCB brings together a diverse range of unique expertise in microbial cell biology. Members of the CMCB investigate both model and non-model organisms, bacteria and archaea, pathogens and non-pathogens.

Assistant Professor at the Metabolomics group, LUMC, The Nederlands

PhD Defence

Source: Nature Biotechnology, Volume 2014, Issue June (2014)

Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive.

Vaccination via the skin or the mucosae

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

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.

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

Can animal venoms yield novel antimicrobial peptides?

The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered…

Animal Sciences’ contribution to the Bioactive Molecules research theme includes research on molecules from natural sources, such as plants, insects, and snake venom, with the aim to identify novel anti-cancer, anti-inflammatory, anti-microbial, and anti-diabetic agents.

PhD at Leiden University and Bruker - the Netherlands

Streptomyces are filamentous bacteria that produce more than two-thirds of known antibiotics.