Bacterial adhesins in host-pathogen interactions

Bacterial pathogens colonize their host organism as part of their infection strategy by recognizing tissue specific antigens. This interaction is mediated by adhesins found on extracellular side of the bacteria. Adhesins are proteins with a complex three-dimensional structure that serves to recognize specific antigens and thereby attach the bacteria to the right target. Bacterial adhesins constitute important targets in antibiotic drug and vaccine developments.  

Aim: This project focuses on determining the three-dimensional structure of bacterial adhesins together with their specific antigen using X-ray crystallography. This will reveal the molecular mechanism by which they interact and will allow experiments directed toward blocking the interaction with other molecules, i.e. development of a drug. The project is suited for students with a keen interest in protein structure-function, host-pathogen interaction and structure guided drug design. 
 
Methods: The project will involve large scale expression of recombinant protein produced in Escherichia coli, protein purification, crystallization and structure determination by X-ray crystallography. The X-ray crystallography will utilize the in-house diffractometer and beam-time at the powerful ESRF synchrotron in Grenoble, France.  We will include complementary biochemical and biophysical methods in order to validate significant findings from the protein structure. If possible, a protocol for efficient identification of small molecule inhibitors of antigen recognition will be developed.  
 
About the group: The candidate will work in the structural biology group at the Department of Chemistry under the supervision of Professor Ute Krengel and Dr. Kaare Bjerregaard-Andersen. The group currently consists of 4 PhD students and 3 Post Docs. In addition, the project involves a collaboration with the laboratories in Hamburg, Germany, and in Stockholm, Sweden.
 
For any questions, or more detailed information concerning this project, please contact by email: 
Professor Ute Krengel 
ute.krengel@kjemi.uio.no
Post Doc.Kaare Bjerregaard-Andersen
kaarebj@kjemi.uio.no
 

Published Mar. 22, 2018 10:29 AM - Last modified Apr. 19, 2018 8:13 AM

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