The Netherlands suffers from high nitrogen emission and one of the major industrial pollutants is NO2. Unfortunately, it proves difficult to locally measure NO2 levels on the ground, but even more so in the earth atmosphere. In GELSONDE, we propose a novel, low-cost and portable NO2 sensor that we will build with a team of materials chemists and sensor specialists. The new sensor is able to accurately measure NO2 levels anywhere on the ground, as well as on high altitudes.

In this project, we will develop new drug development technology based on unique spicrocyclic molecules, to influence so-called protein-protein interactions in the cell. Protein-protein interactions are very common in the cell and their malfunctioning leads to diseases. Using computer modeling, synthesizing libraries of spirocyclic compounds and screening for biological activity, new molecules are being identified that could be on the basis of future drugs.

Galactooligosaccharides (GOS) are used in infant formula to boost the low oligosaccharide content of bovine milk (~0.05g/L) compared to human milk (~20g/L). GOS have been shown to be beneficial to infant health (e.g. improving gut microbiota composition softening stools and modulating immunity and are prepared enzymatically using a selected β-galactosidase, at a high lactose concentration. It is estimated that the GOS mixture produced in this way consists of >75 oligosaccharides at a varying percentage but the exact composition is unknown. Although the health benefits of the overall GOS mixture used as a nutritional ingredient are well established, it is less clear which components are responsible for the effects on infant health. In very rare cases the consumption of GOS is reported to lead to an allergic reaction in older children and adults with pre-existing allergies mainly in the Southeast Asian region. Again, the molecular complexity of GOS complicates the identification of the allergenic GOS components. Recently, primary sensitization against GOS in Singapore has been traced back to an allergic reaction against an unknown glycan found in tropical house dust mite Blomia tropicalis (unpublished results). The aim of this proposal is to develop new methods to isolate and characterize GOS components from a complex GOS mixture. In addition, new methods to prepare well-defined synthetic galactooligosaccharides are proposed. Combined, these methods will lead to the elucidation and preparation of the oligosaccharide structures found in GOS. These compounds will be used to evaluate which oligosaccharides contribute to health and which are allergenic. Finally, new methods are proposed to elucidate the molecular glycan structures in tropical house dust mite Blomia tropicalis responsible for primary sensitization. Overall the proposed work will contribute to the development of next generation GOS mixtures with increased health benefits and reduced allergenicity.

Radboud University and the company Enzyre are joining forces to efficiently identify complex detection molecules (peptide substrates) that can be used to readily measure the activity of enzymatic reactions in blood coagulation. Currently, a labor-intensive process is used to synthesize and test these chemoluminescent peptide substrates, which emit more light the more active the enzyme is. In this project, we propose an innovative new synthesis method by which large numbers of detection molecules are synthesized in parallel, and then tested, after which suitable molecules can be further optimized for application in a diagnostic assay.

The aim of the proposed research is to develop new methodologies to enable the synthesis of complex carbohydrates on a solid support. Complex carbohydrates are very important molecules that are involved in a myriad of biological processes and can even be used as drugs against infective diseases. At present it is not possible to make all types of carbohydrates on solid support. It is important to be able to make carbohydrates on a solid support because only then, these molecules can be made in a fully automated fashion by a synthesis robot. This automation will drastically cut down the time needed to prepare these molecules. The newly developed methodologies will be used to prepare glycans from pathogenic bacteria that cause food borne disease on a solid support. Finally, these glycans will be used to diagnose such an infection and even create vaccines against it.