Elucidating the function of host cells during infectionGCOE Program Seminar(Global Education Seminar)

Infection is the result of specific interactions between pathogens and host cells. Thus, factors on both pathogen and host side are critical for the initiation and progression of an infection. Consequently, inhibition of host factors might enable the prevention or elimination of an infection, thus, constituting an alternative or supplement to conventional antimicrobial drugs. While investigations of virulence associated factors on the pathogen side have been successfully performed for many years, a breakthrough for studying the role of host cell factors has only recently been achieved with the discovery of RNA interference (RNAi). Silencing of gene expression by RNAi has proven to be a robust and straightforward approach towards gene function analysis. Synthetic small interfering RNAs (siRNAs) comprising short 21 to 23 nucleotide long double stranded RNAs, can be used to transiently ‘knockdown’ gene expression in cultured cells for loss-of-function analyses. It is thus possible to study the infection process in human cells by silencing any gene within the whole genome using a variety of high-throughput settings. Interfering with host cell factors and processes critical for pathogen infection, including receptors and innate response mechanisms, and the silencing of factors facilitating pathogen accommodation and replication inside host cells, bears considerable therapeutic potential. Thus, the identification and targeting of suitable host cell determinants and processes promises to present new, and as yet unexploited, ways of treating both acute and chronic infections. Examples of the approach taken include Chlamydia species and the Influenza virus.