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Innate immune evasion by bacteria

Thursday 16 April 2009

Project
Innate immunity is the first line of host defence and consists of soluble and cellular components that recognize common patterns from invading pathogens. Phagocytes and the complement system are crucial components of the innate immunity that take care of efficient elimination of invading bacteria. Although highly effective and efficient, bacteria developed counter measurements to combat the host defence to spread and survive within the host. We study not only innate immune defence mechanisms, but also the tricks that bacteria use to circumvent the host defence arsenal. We focus mainly on innate immune evasion by bacterial excreted proteins. Identification of the bacterial protein and/or the host defence target is the first goal. The annotation of a function to unknown bacterial protein or a new function to known protein aids in the understanding of the pathophysiology of bacterial infections. On the other hand, the bacterial protein will lead to a better understanding of that particular part of the innate immune response. In the far future some of these newly described bacterial proteins may lead to the development of new anti-inflammatory drugs that can be applied in diseases with a strong inflammatory component.

Several strategies are followed to find and identify new bacterial (secreted) proteins that all depend on a multitude of in vitro functional assays covering human phagocyte and complement physiology. Immune evasion molecules are discovered based on the bacterial gene or protein (homology to other proteins, location within the genome on pathogenicity islands) or on the host defence function by starting with an important receptor or function. Starting material can be a simple rough or partially enriched supernate from growing bacteria or a purified recombinant protein. Both strategies have there proís and contraís but proved to be successful in the past. Staphylococcus aureus is one of the bacteria of interest and is also subject of other research projects in the Medical Microbiology related to antibiotic resistance, molecular epidemiology in human (and cow and pig) and genome profiling. But depending on the target, many other bacterial species are tested for the presence of immune evasion molecules. Although our focus for the innate immune system is on phagocytes (particularly neutrophils) and the complement system (both human) other aspect (or species) of the host defence mechanisms are studied as well.

The major research lines study the intervention with: A) the complement cascade; B) leukocyte adhesion and migration events; C) chemokine receptor-mediated cell functions; D) Complement- and Fc-Receptor-mediated cell functions; E) TLR-mediated cell activation. These projects focus on both the function and regulation of the specific host defence pathway as well as the bacterium using cell physiology, protein chemistry, molecular biology (in bacteria and eukaryotes) and some animal experiments. The research group is headed by Prof. Dr. Jos van Strijp and involves senior staff members, post-docís and phD students with their own and overlapping research project.

Techniques
Moleculair biology (protein expression, receptor expression, gene regulation, knock-outs, mutagenesis, in both bacteria and cell lines), cell biology (isolation, culture, functional assays), protein biology (purification, SDS-PAGE, Western, ELISA, Biacore, Seldi-Tof), general microbiology, flow cytometry.

Duration
6 or 9 months

Contact
Dr. Kok van Kessel, tel. 088 75 599 62, k.kessel@umcutrecht.nl

More info
Website UMC Utrecht - Medical Microbiology

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