Background

    The discovery of antibiotics in the first half of the 20th century triggered the development of many anti-infectives. These collectively enabled the treatment of most infectious diseases, thus greatly reducing morbidity and mortality. However, due to the increasing emergence of (multi-)drug resistant pathogens and a simultaneous draining of development pipelines for conventional anti-infectives in the pharmaceutical industry, we are now in danger of facing a post-antibiotic era. There is thus an urgent and unmet need for the development of innovative approaches to treat infectious diseases. TargetInfectX aims at using RNA interference (RNAi) by small inhibitory RNAs (siRNAs) to (i) indentify human proteins as general targets for anti-infective intervention and (ii) to evaluate the potency of specific siRNAs for anti-infective treatment.

    TargetInfectX builds on the results and knowledge gained during InfectX RTD project (2009-2013) but will have far reaching goals. Within InfectX we have acquired a large RNAi dataset for infection of human cells by various pathogens and developed models to interpret such data. However, to date we have explored only a fraction of the phenotypic information present in our image-based assays. We will thus extract a rich set of phenotypic features on the single-cell level to identify human proteins linked to basic cell behaviors involved in the response to pathogens intrusion. Moreover, we realized that siRNA provide potent multi-pronged perturbations of cellular functions which may have therapeutic potential. On the translational side, we will then explore the potential of siRNAs as novel combination therapy to treat infection in appropriate animal models.

 

General Goals

    This project aims at using RNA interference (RNAi) and complementary technologies to comprehensively discover and understant the roles of human factors involved in pathogen infection and to test whether combinatorial knock-down of human factors by individual siRNAs can effectively interfere with pathogen infection

 

Specific Goals

  Analysis of multiple phenotypic features on the single-cell level inorder to establish links with molecular pathways relevant to the infection process

  Exploration of off-target effects and gene regulation mediated by siRNA seed sequences

  Deconvolution of on and off-target effects to map genes to specific phenotypes

  Expansion of the knowledge gained to in vitro and in vivo models in order to discover new ways of fighting infection

  Collaboration with external partners via a platform