Next-generation technologies for studying host-pathogen interactions: A focus on dual transcriptomics, CRISPR/Cas9 screening and organs-on-Chips.

Abstract

Pathogens constantly interact with their hosts and the environment, and therefore have evolved unique virulence mechanisms to target and breach host defense barriers and manipulate host immune response to establish an infection. Advances in technologies which allow genome mining, gene editing such as CRISPR/Cas9, genomic, epigenomic and transcriptomic studies such as dual RNA-seq, coupled with bioinformatics, have accelerated the field of host-pathogen interactions within a broad range of infection models. Underpinning of the molecular changes that accompany invasion of eukaryotic cells with pathogenic microorganisms at the intersection of host, pathogen and their local environment has provided a better understanding of infectious disease mechanisms and antimicrobial strategies. The recent evolution of physiologically relevant three-dimensional (3-D) tissue/organ models and microfluidic organ-on-chip devices also provided a window to a more predictive framework of infectious disease processes. These approaches combined hold the potential to highly impact discovery of novel drug targets and vaccine candidates of the future. Here we review three of the available and emerging technologies-dual RNA-seq, CRISPR/Cas9 screening and organs-on-chips, applicable to the high throughput study and deciphering of interaction networks between pathogens and their hosts that are critical for development of novel therapeutics.