Analysis of gene expression in infectious diseases - development of tools for tomorrows therapeutics

The major objective of this project is to provide basis for the development of effective therapies
against microbial infections currently affecting human and animal health worldwide. This will be
achieved by an analysis of the molecular processes in vivo in both host and pathogen during
infection. The porcine lung disease pleuropneumonia caused by Actinobacillus pleuropneumoniae
(Ap) is used as a model for bacterial infection in a mammalian host.
Based on in vivo infections of pigs by pathogen strains of low and high virulence, the link between
bacterial virulence, genotype and gene expression will be determined and a correlation to the host
expression “phenotype” and other host factors (e.g. genetic background, immunological status,
physiological status) will be established. This will enable development of new tools for control of
infectious diseases in mammals. The specific objectives of this project are
1. Characterise two serotypes of Actinobacillus pleuropneumoniae (Ap) by full genome
sequencing and annotation.
2. Design and produce full genome microarrays targeting Ap strains of both high and low
virulence.
3. Analyse the span of genetic variation between Ap strains of different serotypes by
comparative genome hybridisation and sequence analysis of variable regions.
4. Conduct in vitro infections of porcine lung epithelial cells with two serotypes of Ap and
study the complex interplay between pig and Ap cells during infection and transcriptional
variation between the two serotypes.
5. Conduct in vivo experimental infection of pigs with two serotypes of Ap and study the
molecular processes occurring simultaneously in both pig tissues and Ap by microarray
expression profiling and real time quantitative PCR.
6. Combine the results and describe the fundamental molecular processes occurring in both
host and pathogen during infections and thereby provide a scaffold for the development of
effective therapies against microbial infections in mammals.