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

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.

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

PURPOSE: In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products.

A major challenge in the formulation of biopharmaceuticals is to overcome their inherent instability during production, storage, transportation, handling and administration. We are studying underlying mechanisms of degradation of biopharmaceuticals (including therapeutic proteins, vaccines and advanced…

Promotors: W. Jiskoot; G.J. Witkamp, Co-promotor: M.R. Nejadnik

Formulation of biopharmaceuticals

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…

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.

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.

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

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

Developing robust and comprehensive analytical methods to size and quantify subvisible particles in biopharmaceutical products.

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.

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

Vaccines are an extraordinary category of biopharmaceuticals. They are usually prophylactic and come in many types, from whole bacteria to peptides and nucleic acids. They are very cost effective and almost every human on the planet is vaccinated. The latter mandates that vaccines have to be extremely…

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…

Promotoren: G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

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)…

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

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

Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be…

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

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

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

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

PhD Defence

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.

Hass

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

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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…

Promotor: Prof.dr. M. Ubbink

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.

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

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

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

Promotor: A. Kros

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

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.

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.

Supervisor: P.J.J. Hooykaas

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,…

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.