Exjobbsförslag från företag

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Förslaget inkom 2004-06-29

PHAGE AS THERAPEUTIC AGENTS

OBS! ANSÖKNINGSTIDEN FÖR DETTA EXJOBB HAR LÖPT UT.
Increasing antibiotic resistance in pathogens necessitate development of alternative treatments. Phages (bacterial viruses) are natural predators on bacteria, and a very large quantity of empirical data from the former Soviet Union indicate that treatment of various human infections with phages can be very successful. However, neither these investigations nor subsequent model studies in the West addressed properties of phage important for success. Despite the present-day intimate knowledge of phage development under laboratory conditions, there is still little if any scientific basis for understanding the interaction between phages and their hosts in the setting of a human or animal body. Such a basis is imperative to permit our society to use phages successfully to prevent and combat infectious disease.
We have isolated human E. coli strains from patients with urinary tract infections and diarrhea, and tested these with different T4-like phage. Results sofar indicate profound differences in phage development depending primarily on the host infected. The goal of the present project is to determine what causes these differences, and what makes phage successful predators of different hosts in infection under conditions mimicking those in the human gut. This will be done by analyzing mRNA differential display, and isolating and characterizing mutants able to kill bacteria more or less efficiently than wild-type phage under the tested conditions.
Methods employed include anaerobic cultivation, biological infectivity assays, mutagenesis and mutant analyses, RNA isolation, Northern blots, PhosphorImager quantification.


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