Lateral Strategies for Scientists and Those Who Study Them

The thesis Adapting in the Knowledge Economy investigates the strategies deployed by academic scientists when trying to adapt and maneuver within an increasingly complex mixture of scientific, industrial and governmental agendas. Chapter one “From insights to invoice” summarizes the last decade of Danish research policy as a tendency towards intensified focus on interaction between the university and “outside” actors. Looking at Danish policy documents and interview data the chapter shows how policy changes responded to an idea of “ivory tower” researchers isolating themselves in Danish universities. Furthermore, the interaction agenda was motivated by the perception that knowledge was produced but not sufficiently used. Strongly influenced by the concept of the knowledge economy and that of mode 2 knowledge production, policy changes were directed at bridging a gap between the producers and the consumers of knowledge. A series of reforms and initiatives were launched to facilitate more interaction between science and industry as well as more responsiveness towards societies’ problems on behalf of the universities. This interaction agenda was coupled with an increase in the economic investment in research and an increased focus on competition between researchers in order to ensure high quality in knowledge production...

A Role for the RNA Chaperone Hfq in Controlling Adherent-Invasive Escherichia coli Colonization and Virulence

Adherent-invasive Escherichia coli (AIEC) has been linked with the onset and perpetuation of inflammatory bowel diseases. The AIEC strain LF82 was originally isolated from an ileal biopsy from a patient with Crohn's disease. The pathogenesis of LF82 results from its abnormal adherence to and subsequent invasion of the intestinal epithelium coupled with its ability to survive phagocytosis by macrophages once it has crossed the intestinal barrier. To gain further insight into AIEC pathogenesis we employed the nematode Caenorhabditis elegans as an in vivo infection model. We demonstrate that AIEC strain LF82 forms a persistent infection in C. elegans, thereby reducing the host lifespan significantly. This host killing phenotype was associated with massive bacterial colonization of the nematode intestine and damage to the intestinal epithelial surface. C. elegans killing was independent of known LF82 virulence determinants but was abolished by deletion of the LF82 hfq gene, which encodes an RNA chaperone involved in mediating posttranscriptional gene regulation by small non-coding RNAs. This finding reveals that important aspects of LF82 pathogenesis are controlled at the posttranscriptional level by riboregulation. The role of Hfq in LF82 virulence was independent of its function in regulating RpoS and RpoE activity. Further, LF82Δhfq mutants were non-motile, impaired in cell invasion and highly sensitive to various chemical stress conditions, reinforcing the multifaceted function of Hfq in mediating bacterial adaptation. This study highlights the usefulness of simple non-mammalian infection systems for the identification and analysis of bacterial virulence factors