Projects

In this work, we will advance reactive molecules ('probes') for the study of proteins. The need for development of new probes stems from the fact that different types of probes bind diverse proteins. Once a protein is tagged, it can be analyzed and identified, and in cases where the enzyme appears to play a role in human diseases, a drug candidate can be developed based on the employed probe. The approach in this project is novel in the ...

For its immune system to function properly, the human body relies on a multitude of signaling processes executed by many different types cells. The most common one of these cell types is the neutrophil. Neutrophil cells patrol the blood and once encountering pathogens, they react to kill it making use of their armory contained in different types of granules. The neutrophil serine proteases are an important part of this armory and they can, ...

Classical proteomics experiments do not distinguish between active or inactive enzymes, yet only the active forms are responsible for biochemical transformations. Activity-based proteomics solves this problem by marking active enzymes with chemical tools termed activity-based probes (ABPs). Although ABPs have been developed for a variety of enzyme targets, their chemical synthesis forms a bottleneck.

In this research proposal, we will ...

Proteases are enzymes that cut proteins by catalyzing the hydrolysis of the peptide bond. They can be found in almost every organism, where they play a part in many biological pathways and are involved in various human diseases. For example, cathepsins, a class of cysteine proteases, are upregulated in various cancers, making them an interesting biomarker and suitable targets for tumor labeling.

An excellent method for the detection of ...

Bacterial infections continue to be a threat to the well-being of mankind. As a result, there is a pressing need to find new protein targets for next-generation antibiotics. Bacterial signal peptidase I is an essential serine protease with an unusual catalytic machinery. It is involved in the secretory pathway and is considered a potential future drug target. In this project, we will set up an assay for this protease and screen an in-house ...

Proteases are involved in many highly regulated biological processes, such as apoptosis, cell-cell communication and blood coagulation. Inhibitors and activity-based probes (ABPs) have been successfully utilized as chemical tools to study these enzymes. However, when studying fast and dynamic processes, local and temporal acivation of these reagents is desirable. Such reagents can first of all be used for basic study of these processes, but ...

Modulation of adipogenesis is one of the most promising targets in the search for therapies against obesity. Given the large lipid pool present in adipocytes, it is likely that protein (de)palmitoylation plays a role during their differentiation. However, this post-translational modification is understudied in this process. In an in vitro model of adipogenesis, I therefore aim to (1) identify the substrates that are (de)palmitoylated, (2) ...