My research focuses on the organic synthesis of chemical tools and their use in the study of biological processes. Compound libraries encompassing biologically active molecules are synthesised and used, both in-house and through collaborations with biological/biomedical researchers, to study physiological processes in glycobiology and immunology. The libraries include activity-based probes that react with enzymes (proteases, glycosidases) and are tagged for directed proteomics studies. Students interested in the synthesis of biologically active molecules and also in their analysis in a biological setting are invited to join my research group.
My research focuses on the synthesis of well-defined fragments of the biopolymers, specifically carbohydrates and nucleic acids (DNA, RNA). Key synthetic transformations (glycosylations, phosphorylations) are studied in depth with the aim to develop procedures to obtain optimal results (yield/stereo selectivity) in the preparation of the target compounds. These are selected from nature on the basis of structural challenges and biological relevance. Students interested in the development of fundamental synthetic methodology and in the preparation of complex molecules with biological potential and that have not been prepared before are invited to apply for an internship.
My research focuses on fundamental and applied synthetic carbohydrate chemistry. I aim to develop robust glycosylation strategies that enable the interconnection of monosaccharides of different nature. The synthetic methodology is applied in the parallel synthesis of oligosaccharide libraries for biological studies, and both solution phase and (automated) solid phase oligosaccharide assembly methodologies are studied. The compound libraries are evaluated on their immunological properties in collaboration with researchers at the LUMC. My ultimate research objective is to develop a synthetic vaccine in which carbohydrates are a major component.
Metal-containing molecules are widely used in chemical biology and nanotechnologies. They combine geometrical features and a chemical (photo)reactivity that are difficult to achieve with organic chemistry. My research focuses on two different themes: light-activated anticancer prodrugs, and biomimetic photocatalysis. In the first one, I use light to activate anticancer metallodrugs inside a cell. Achieving selectivity in anticancer research, ie, killing cancer cells without killing healthy cells nearby, is a difficult challenge. Using light to decide when and where a molecular compound will start interacting with proteins or DNA, ultimately to kill a cell, is a promising approach lying at the crossing point between medicinal inorganic chemistry, photobiology, and optics. My second research field is related to solar fuels: I investigate whether it is possible to use metal-based catalysts to store the energy of visible photons into a chemical bond.
The research in my group consists of three major research themes: 1) model systems for liposome-cell fusion, 2) silica nanoparticles based controlled release systems and 3) targeted drug delivery systems based on hydrogels. Typically a research project within my group consists of the design and synthesis of the molecules of interest and/or the physical characterization of the (self-assembled) systems. For this we use a wide variety of techniques like NMR, CD, cryo-(TEM), SEM, IR, ellipsometry and fluorescence spectroscopy. In collaboration with other groups the interactions of our materials with cultured cells and/or zebrafish are studied. These and other projects cover the entire spectrum of purely fundamental research to applied research, so there always will be a project that matches your interest.
The research of my group focuses on developing new chemical tricks to study and manipulate the immune system. We are particularly interested in the field of therapeutic cancer vaccination: where we try to harness a patient's own immune system to fight off an existing tumour. To achieve this, we make new compounds and test these in model vaccines. We also study the biochemical changes our compounds induce in great detail. The techniques we use are a combination of organic synthesis, cell biology and immunology. As such we have positions for chemistry and life science students with an interest in immunology.
The research in my group focuses on two fundamental aspects that need to be characterized in order to use graphene as an ideal sensor material: i) how to effectively interface graphene devices with biological materials so that detection becomes sensitive and selective, and ii) understand and characterize the chemical reactivity of ‘just made’ graphene edges. Exploiting the full potential offered by graphene as a natural material in sensing applications will only be possible through in-depth fundamental research of these two limiting aspects.
In a multidisciplinary research line, in which organic and medicinal chemistry are combined with molecular biology and chemical biology, we aim to a) develop assays to determine the activity of proteins, and b) to design, synthesize and characterize small molecules that act as chemical tools to visualize and control protein activity. We use computational chemistry together with activity-based probes for compound profiling and optimization. In (inter)national collaborations with biologists and pharmacologists we test our molecules in preclinical models of disease. Our current projects focus on kinases and proteins of the endocannabinoid system.
Regenerative medicine holds the promise to solve the unmet need of repairing or replacing damaged tissues and organs lost due to age, injury or disease. In order to stimulate the growth of tissues or organs, a material that can mimic the natural extracellular matrix, both biophysically and biochemically, is required. Despite significant advances in the biomaterials field, many important questions still remain, such as: how to make a material that is stable and biocompatible, yet can provide a range of mechanical properties to replicate a specific cellular environment? Moreover, what are the ideal biomolecules to use in these scaffolds to mediate a specific cellular process? Our group looks at how to address these questions through the preparation of (supra)polymeric materials with bioactive moieties and, most importantly, studying how they interface with cells. Projects within the group are highly interdisciplinary, ranging from synthesis of materials to characterization and cell-culture.
The genomic DNA of every organism needs to be organized and compacted in order to fit inside the cell. This is achieved by the joint action of numerous architectural proteins that aid in folding the genome. Genome folding is tightly interconnected with transcription, with genes in certain regions being silenced, while others are highly transcribed. Our interest lies in understanding how architectural proteins act on DNA and how they regulate transcription. We investigate the activity of these proteins in vitro as well as in vivo using biochemical and state-of-the-art biophysical approaches.
Understanding biological phenomena often requires knowledge of processes at a molecular level. The full elucidation of a molecule's function frequently demands its three dimensional structure. The predominant method for determining the atomic coordinates of macromolecules is X-ray crystallography. Our research involves developing new computational methods to determine crystal structures more efficiently and when existing methods fail. In collaboration with others, including groups in the Leiden Institute of Chemistry and the LUMC, we apply X-ray crystallography to determine the structure of medically relevant proteins.
Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man.The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level to increase understanding of biochemical processes in health and disease. Ultimate proof of insight is discovery of applicable biomarkers and rational design of effective therapeutic interventions for metabolic disorders. We aim to further accomplish these by multidisciplinary research in (inter)national collaboration with experts in different fields.In recent years, chemical biology and analytical chemistry have increasingly expanded our research tools. Our current work focuses on glycosphingolipids and their metabolizing enzymes, a topic relevant for lysosomal storage disorders, neurodegenerative disease and metabolic syndrome.
Proteins have to form complexes with DNA, other proteins and small molecules. We investigate how protein complexes are formed and what they look like at the atomic level. We have shown that some complexes are dynamic and we try to make a ‘movie’ of their interactions. We also determine how small molecules travel through an enzyme to reach the active site. This requires 'breathing' of the protein structure. When you consider such dynamics as an inherent property of proteins, the structures come to live. This research is so fascinating because it studies biomolecules really at the atomic level. It brings together physics, chemistry and biology to elucidate the physical-chemical properties that dictate how proteins work.
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