PARTNER N°

25

NAME OF INSTITUTION

Max Planck Institute for Infection Biology

BRIEF DESCRIPTION OF THE TEAM
 

Owing to the intimate co-evolution of pathogens and hosts, the relationship between these poles has reached an unprecedented complexity; the immense diversity of pathogenic microorganisms is echoed by an extremely complex, yet fine-tuned host response system. In order to gain a holistic understanding of the networks conveying the cross-talk between a pathogen and host cells during the course of an infection, we aim to assess the functions of both pathogen and host cell determinants at an unbiased, global scale. This includes loss-of-function studies, transcriptional profiling and comparative protein mass-spectroscopy. Current emphasis is placed on the analysis of crucial host cell determinants by high-throughput, automated RNA interference screens. Using bioinformatics approaches to connect data sets collected from varying perspectives of the pathogen-host cell interaction, we generate a comprehensive and time-resolved view of an infection and define signaling hot-spots and central targets for intervention.

 

KEY CONTACT PERSON(S)

Key scientific contact person 1 (Team leader)

Name

Prof. Dr. Thomas F. Meyer

Photo

 

Position in the Institution

Professor and Director

Email address

meyer@mpiib-berlin.mpg.de

Phone number

+49-30-28460-400/-402

Mobile phone number

 

Postal address

Charitéplatz 1

D-10117 Berlin

GERMANY

 

Role in the Consortium

WP: 4

Task: 4.5 Identification of ZIKV relevant host factors by global loss‐of-function‐

screens

Sub-task:

Subtask 4.5.1: Characterization of the cell lines used for the screen

Subtask 4.5.2: siRNA screen

Subtask 4.5.3: Validation of the siRNA screen

Role:

The aim of this task is to identify cellular factors by performing genome-wide RNAi and CRISPR/Cas9 screenings. Therefore, adequate human cell lines and conditions of ZIKV infection required for the screen will first be defined and suitable reporter viruses (e.g. expressing eGFP) will be characterized, and conditions of infection defined. Positive and negative siRNA controls for the screen will be established. Functional assays will be set up for the arrayed loss‐of‐function siRNA screens. A ZIKV siRNA loss‐of‐function screen will be performed on one cell line with approximately 60,000 siRNAs. A fully automated screening procedure will be developed. Screening hits will be validated by (1) additional, independent siRNAs and (2) by using CRISPR/Cas9 gene knockouts. Primary cells including host cells naturally infected by ZIKV, such as neuronal and placental target cells, will also be used to analyze the impact of the identified factors in the most relevant cellular models. In addition, we will perform CRISPRa based gain‐of‐function studies to assess if overexpression of selected antiviral genes influences ZIKV replication. To further validate targets, chemical compounds targeting the identified host cell factors will be tested in vitro using the established cellular HTS‐assay and drug candidates will be investigated using appropriate animal models.