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Glycobiology of microbe/host interaction
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Scientific project
Glycans and lectins are prominent components of microbial cell walls and membranes and most often are the first contact platform with the host cell during infection processes. The interactions involving lectins and/or glycans from the microbial membrane or cell wall and their cognate interacting partners from the host cell membrane are of weak affinity but are crucial for establishing the first contact for invading the host. In the past, these interactions have received little attention partly for their weak affinity, but also because of a lack of powerful biochemical tools to investigate them. In recent years, achievements in the fields of both chemoenzymatic and chemical syntheses have significantly boosted the field of glycobiogy by providing homogenous and fully characterized material for biochemical investigations. Our laboratory focuses around two goals.
Role of Glycan-lectin Interaction During Invasion of Erythrocytes by the Malaria Parasite Plasmodium falciparum
Malaria is a major cause of mortality and morbidity in the world and leads to 2 Million deaths annually. Despite many efforts, no final therapeutic solution has been developed to fight the disease. The life cycle of Plasmodium falciparum, the agent responsible for more than 90% of the Malaria cases, involves a blood stage in which the parasite resides and multiplies in red blood cells. One important research focus for developing anti-Malarial drugs is the invasion step of the erythrocyte by the freshly released merozoites. Although many proteins with diverse functions in the process of invasion have been reported the overall scheme of the invasion process has not been completely solved. It’s known that glycosylated proteins on the membrane of red blood cells are important for the internalization of the parasite, with the glycan moiety playing a critical role. In addition, glycan structures on the parasite’s surface might also be involved in the process. Our focus is to understand the actual function of the glycan structures on both host and parasite membranes in order to help clarify the molecular mechanism of the invasion process, using biochemical and cell biological means.
Applying Phage display Technology to Select and Develop Peptide Mimotopes of Glycan-based Anti-parasitic Vaccines
The development of carbohydrate-based vaccines represents an interesting alternative to other vaccine development strategies. Since Carbohydrates are not primary gene products, modification of a given glycan epitope by a microorganism in order to escape host immune response should be more challenging compared to peptide epitopes. Carbohydrate-based vaccines therefore become very attractive for fighting pathogens like parasites, which constantly reshuffle their antigenic pool by genetic variation. Although it has become evident that, when coupled to a carrier protein a formally non-immunogenic glycan epitope can become a good antigen, the immune response remains generally weak compared to an immune response against peptides or proteins. We are using phage display technology to identify and characterize peptide mimotopes of glycan antigens in order to empower the host response against carbohydrate epitopes.
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| © 2012, Max-Planck-Institut für Kolloid- und Grenzflächenforschung, Potsdam |
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