Are you a Life Science & Technology student and do you want to perform your research internship in another research group of the Science faculty, Leiden University Medical Centre (LUMC), Dutch Cancer Institute (NKI) or Erasmus Medical Centre (ErasmusMC)? Apart from the external supervisor, you also need to have a mentor at the LIC, who must be one of the LIC Principal Investigators (PIs). For LST students doing such an ‘external’ internship the mentor can be one of the members of the LIC Education team (Noteborn, Brouwer, Goosen) as mandated by PI and ‘formal mentor’ prof.dr. Lies Bouwman. If appropriate, please contact prof.dr. Lies Bouwman.
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.
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.
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.
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.
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.
A sophisticated regulation network in plants and algae prevents them from photodamage, but also sets an upper limit for the production of biomass or biofuels. A major quest is to gain molecular control over this network and push the limit. Photosynthetic light-harvesting proteins are key players here that can switch ‘on and off’ and control how much of the incoming sunlight is used. In a new group in the SSNMR department, I aim to investigate the plasticity of the involved proteins, atomic-level pigment interactions and the influence of a membrane environment. A research project in my group may involve solid-state NMR and DFT, preparation of protein-reconstituted lipid nanodiscs or development of a cell-free expression system. Hence, there are possibilities for physical, biochemical or molecular-biological oriented students with an interest in bio-energy research.
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.
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.
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.
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.
At the heart of the cell, in the nucleus, proteins and nucleic acids come together to maintain and express our genetic information. The interplay of proteins and nucleic acids in both genetic and epigenetic pathways forms the research focus in the Van Ingen group. How do their structures, motions and interactions come together to elicit function? The group’s main research line is centered on the molecular basis of chromatin function at the level of its repeating unit, the nucleosome.
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.
Discover the world at Leiden University