- Overview
This is our real world, the world of science. In our daily life we try to get our PhD in cell biology, working together with a team of enthusiastic young scientists, trying to increase our understanding in the processes that intrigues us most, those that happen in our own body. Using state-of-the-art techniques we try to answer questions like why things go wrong during breast cancer treatment, how bacteria hide for our immune system, and how cells dispose their garbage. Read on to learn more about the projects we are working on, and what keeps us busy during the day...
- Estrogen Receptor
The estrogen receptor is a member of the nuclear hormone receptor superfamily, and plays an important role in the development and maintenance of the sexual reproductive tissues. Not surprising, this receptor plays a key role in many tumors derived from these tissues as well. Therefore, estrogen receptor-positive breast cancer patients are commonly treated with tamoxifen, a potent and widely used anti-estrogen. Resistance to this drug forms a major problem in the clinic however. To study the mechanism by which the receptor can become drug-resistant, we have developed a sensitive assay that allows us to directly visualize the changes the receptor undergoes upon drug binding. | Learn more >>- MHC Class II antigen presentation
Our immune system continuously monitors signals presented by the cells in our body that might identify suspicious behaviour, like a viral outbreak, bacterial infection or tumorigenic cell growth. When it does locate any of these, it can take effective countermeasures wherever necessary to prevent further spreading. The MHC Class II antigen presentation pathway allows cells to sample the content of material taken up from their environment, including hazardous bacteria. Proper functioning of this pathway involves many steps and a number of dedicated proteins that play a key role in determining a potential immune response. Using sensitive microscopic techniques, we can now visualize and investigate these crucial steps inside living cells. | Learn more >>- Ubiquitin-Proteasome System
Regulation of endocytosis, gene transcription, and protein degradation, only three of the biological functions of the only 76 amino acids 'big' protein Ubiquitin. With its 8.6 kDa ubiquitin it is not a heavy weight protein, but as its name already mentions, it is ubiquitously expressed throughout cells, tissues, and organisms of great variety. The main and best known function of ubiquitin is to target proteins for proteasomal degradation. Target proteins are malfolded proteins, including both newly synthesized, old, and aggregated proteins. It is of great importance for the cell to get rid of these malfolded proteins, as they form a potential selfdestructive hazard to the cell and ultimately the whole organism. With the help of the specific properties of ubiquitin, including ubiquitination and deubiquitination, many techniques are available not only to study ubiquitin itself, but also to study the fate of DNA constructs with proteins fused to the c-terminus of ubiquitin. | Learn more >>
Mek: "Indeed one could type me as a bit schizophrenic as I work on two quite different subjects. The first involves a receptor extremely important in breast cancer, while the other is all about proper functioning of our immune system. Both projects seem at first unrelated, yet are interconnected through the use of similar techniques. Assessment of individual cells using sensitive microscopic measurements leads us to an important further understanding of the processes involved in both topics."
Tosj: "No, I am not the perfect tool to get annoying persons in the hospital, the code word is: Ubiquitin. Ubiquitin is a protein that is involved in the destruction and recycling of proteins. Not only hightech single cell microscopy techniques for me, but also many biochemical assays to gain more insight into this tighly regulated, but very destructive machinery."