The Protein Centre can supply you with purified proteins that are essential for many experiments, ranging from in vitro inhibitor screening and enzymatic analysis to manipulation of life cells.

How can we develop a new microscope that can distinguish individual atoms in proteins?

We have recently discovered that there are biological proteins that phase separate out of solution much the way oil will de-mix from water (see movie). These form dense, liquid-like phases called protein condensates.

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)…

This thesis describes the use of bioorthogonal proteins in immunological settings. It provides an introduction towards the field of protein modification, which was used throughout the thesis for the expression of proteins containing unnatural amino acids.

Some species of proteins which can form liquid-like condensates, also exhibit growth into fibers (or fibrils). One particularly interesting set of such proteins are those that are associated with neurodegeneration in which the fiber growth may be related to the pathological fibrils observed in disea…

Promotor: Prof.dr. C.A.M.J.J. van den Hondel, Dr. ir. V. Meyer, Co-promotor: Dr. A.F.J. Ram

Promotor: M. Ubbink, Co-promotor: G. Siegal

Promotor: Prof.dr. E.J.J. Groenen

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences…

Hass

For each living organism health is ensured by correct functioning of its cells. Cells therefore have elaborate methods for regulation of their proteins.

Promotor: M. Ubbink, Co-promotor: G. Siegal

Promotor: W. Jiskoot, Co-promotor: A. Hawe

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

Promotor: M. Ubbink, Co-promotor: G. Siegal

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…

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.

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.

Therapeutic proteins have revolutionized the treatment of many severe diseases like multiple sclerosis, haemophilia, diabetes and many more. Unfortunately, even recombinant proteins with structures (almost) identical to those of their endogenous counterparts often induce the formation of anti drug antibodies…

Is translocation of nucleases possible via Agrobacterium T4SS and is it efficient enough for mutagenesis?

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

Bacteria often experience external challenges, such as changes in environmental conditions or attacks by bacteriophages.

The aim of the research presented in this thesis was to develop new methods forchallenging systems in liquid-state NMR using paramagnetic effects generated by thetwo-armed probe CLaNP-5.

Promotor: Prof.dr. M. Ubbink

Science

The close interaction between organic chemi stry and biology goes back to the late 18th century, when the modern natural sciences began to take shape. After synthetic organic chemistry arose as a discipline, organic chemists almost immediately began to pursue the synthesis of naturally occurring compounds,…

The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study.

Supervisor: P.J.J. Hooykaas

The thesis describes the use of electron paramagnetic resonance (EPR) spectroscopy, in continuous wave and pulse modes, to address the interaction of α-Synuclein (αS) with membranes and the aggregation of αS.

Activity-based protein profiling (ABPP, also termed chemical proteomics), is one of the pillars of chemical biology, and at LED3 we have taken it to the next level. ABPP allows the assessment of protein function in live cells and tissues, which means that the activity of a complete protein family can…

The research is aimed at development of an efficient gene targeting method that allows controlled integration of DNA at a preselected site in the Trichoderma genome.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-promotor: B.I. Florea

Supervisor: P.J.J. Hooykaas Co-Supervisor: R. Offringa

In our research protein translocation from Agrobacterium into yeast and plant cells is studied to obtain fundamental insights in the translocation process

In this study, we evaluated the influence of supercritical carbon dioxide (scCO2) spray drying conditions, in the absence of organic solvent, on the ability to produce dry protein/trehalose formulations at 1:10 and 1:4 (w/w) ratios.

The RNA guided endonuclease based on the CRISPR/Cas system of Streptococcus pyogenus is a potent new tool for genome engineering in plants.

Promotor: W. Jiskoot, Co-promotor: H.A. Every

The receptor nomenclature committee of IUPHAR, the International Union of Pharmacology, has several subgroups. Among these are a few that our division is involved in, those for adenosine, nicotinic acid, and GnRH receptors.

Promotor: Prof.dr. M. Ubbink

The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy.

We aim to understand ion homeostasis in the model eukaryote S. cerevisiae.

Promotor: Prof.dr. J. Brouwer, Co-promotor: Dr. Remus Th. Dame

Promotor: A. Kros

The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

Protein–protein complexes are formed via transient states called encounter complexes that greatly influence the formation of the stereospecific complex.

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?

Every organisms in the tree of life faces the same challenge: the length of its DNA exceeds the volume of the cell it needs to fit in. Several strategies have evolved to solve this problem, one of them being the expression of proteins that bind and organize the DNA.

It is estimated that approximately 30% of all proteins require a metal to function. Investigating the relationship between metal-binding and peptide/protein folding allows us to uncover fundamental rules for creating metallo-peptides and proteins, which in turn leads to the creation of new structures,…

PNAS publication on protein encounter complexes