Objective
During my postdoc at a marine biotechnology lab in Newcastle I experienced that bacteria growing in shakeflasks in the lab and bacteria in natural biofilms behave very differently. For instance, the global gene expression and production of secreted proteins is very different between these modes of growth. I would like to bring the knowledge and skills acquired there to a higher level by studying the interaction between a clinically relevant biofilm and host organism. To achieve this, I will study the dynamics of Staphylococcus aureus biofilms in interaction with the human innate immune system in the laboratory of Prof. van Strijp in Utrecht. S. aureus is a Gram-positive coccus that causes life threatening diseases and has become resistant against most antibiotics (MRSA). Our innate immune system is crucial in fighting S. aureus infections. Strikingly, S. aureus evades this defence line by production of small secreted proteins that repress this immune system. In many infections, S. aureus’ growth mode is generally considered to be biofilm-like. Using a novel, biofilm centred approach I will study the interaction between the innate immune system and S. aureus. By comparing planktonic growth with several biofilm stages using proteomic analysis, I will screen for novel immune evasion molecules that are expressed specifically during the biofilm mode of growth of S. aureus. The identified proteins will be studied further using deletion mutants in S. aureus and the proteins will be overexpressed in heterologous hosts, such as E. coli or B. subtilis. Using the mutant strains and the overproduced proteins, the specific interactions of these novel proteins with the innate immune system will be examined, both in vitro and in vivo. The identified molecules will be highly interesting drug targets against a problematic microbial pathogen
Fields of science
Call for proposal
FP7-PEOPLE-2010-RG
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Funding Scheme
MC-ERG - European Re-integration Grants (ERG)Coordinator
3584 CX Utrecht
Netherlands