In order to colonize and cause disease in a susceptible host, microorganisms evolved unique strategies to evade the host immune defense systems. Microorganisms secrete molecules, like proteins, that specifically inhibit different components and pathways of the immune system. Studying these microbial immune evasion strategies will teach us more about the ways microorganimsn interact with the (human) host and how they cause colonization and disease. Understanding the microbial mechanisms of immune evasion will teach us more about the immune system and lead to development of novel therapeutic strategies to modulate the immune system in those diseases where disregulation the immune system plays a pivotal role like sepsis, auto-immune diseases and cancer.
In order to study their unique mechanism of action identifying immune-evasion molecules is an essential but extremely challenging step. We use modern phage display selection strategies to functionally identify new microbial immune evasion molecules. In this technique microbial proteins are expressed on the surface of a bacterial virus, a filamentous bacteriophage allowing (semi)functional selection of proteins for a s
Many immune evasion molecules from human pathogens are human specific. This means they only interact with human immune components, hampering in vivo studies. By introducing random mutations in the immune evasion proteins and screening for binding to non human immune targets we aim to change the host specificity of these immune evasion proteins.
Immune evasion proteins are no suitable for direct therapeutic use. Therefore a third field of research focusses on design of small functional peptides. Using random peptide phage display we try to identify small peptides with similar immune modulating action as the full length protein. We use synthetic biology to introduce non-natural chemically reactive amino acids into these peptides. Using a chemical scaffold we create peptides with a highly constrained 3D defined structure mimicking the discontinuous nature of protein binding sites.