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 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.

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

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

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).

Towards a Biological Understanding of the Middle to Upper Palaeolithic Transition

Pathways of toxicity

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 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

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…

PhD Defence

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

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…

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

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

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.

Can animal venoms yield novel antimicrobial peptides?

PhD at Leiden University and Bruker - the Netherlands

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

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

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.

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…

Molecular Physiology is a research group at the Leiden Institute of Chemistry, headed by Prof. Mario van der Stelt. The research aim is to design, synthesize and apply new chemical tools to answer important biological and medical questions. We use activity-based protein profiling, assay development,…

Can we find new chemical and biological sensing routes on the edge and surface of graphene to improve the potential of graphene to act as a sensor?

The Netherlands X-omics Initiative is a new facility as part of the National Roadmap for Large-Scale Research Infrastructures. It is partly funded by NWO with a total budget of 40 million euro. The project started on September 2018 and will last for ten years.