Joint project
Development of a unique "high-throughput" platform for identification of essential cellular factor for virus replication
Funder: National Veterinary Institute
Period: 2019-2026
URI: https://www.vr.se/english/swecris.html#/project/2018-05766_VR
Detailed description:
Emerging and re-emerging Zoonotic pathogens are challenging human and animal health all around the world, but nonetheless for most of these bio-threats there is no good antiviral treatment available.The identification/characterization of cellular factors exploited by the pathogens are essential for development of novel antiviral drugs.
Emerging and re-emerging Zoonotic pathogens are challenging human and animal health all around the world, but nonetheless for most of these bio-threats there is no good antiviral treatment available. The identification/characterization of cellular factors exploited by the pathogens are essential for development of novel antiviral drugs. To improve the situation, we propose to develop a powerful and unique screening platform that enables to rapidly identify host cell factors that are essentially required by pathogens for infection and replication. By using the power of our developed haploid embryonic stem cells (ESCs) library, where every single gene is reversibly mutated, we will establish an in vitro infection model system, which will facilitate characterization of the essential cellular genes for virus replication. On the top of this, we have recently developed a novel mutagenesis system that allows to map host factor interactions at amino acid resolution, which in normal screens are impossible to find. In addition, we have developed 3D human organoids, which can be the ultimate model for validation of the identified cell factors. Furthuremore We will adapt our already developed microfluidic system to these organoids, which will give us an unique possibility to investigate the function of our identified cellular factors. These tools, in concert, will give us a powerful platform to define and characterize the most essential cellular factor for the virus infection.
Emerging and re-emerging Zoonotic pathogens are challenging human and animal health all around the world, but nonetheless for most of these bio-threats there is no good antiviral treatment available.The identification/characterization of cellular factors exploited by the pathogens are essential for development of novel antiviral drugs.
Emerging and re-emerging Zoonotic pathogens are challenging human and animal health all around the world, but nonetheless for most of these bio-threats there is no good antiviral treatment available. The identification/characterization of cellular factors exploited by the pathogens are essential for development of novel antiviral drugs. To improve the situation, we propose to develop a powerful and unique screening platform that enables to rapidly identify host cell factors that are essentially required by pathogens for infection and replication. By using the power of our developed haploid embryonic stem cells (ESCs) library, where every single gene is reversibly mutated, we will establish an in vitro infection model system, which will facilitate characterization of the essential cellular genes for virus replication. On the top of this, we have recently developed a novel mutagenesis system that allows to map host factor interactions at amino acid resolution, which in normal screens are impossible to find. In addition, we have developed 3D human organoids, which can be the ultimate model for validation of the identified cell factors. Furthuremore We will adapt our already developed microfluidic system to these organoids, which will give us an unique possibility to investigate the function of our identified cellular factors. These tools, in concert, will give us a powerful platform to define and characterize the most essential cellular factor for the virus infection.
Coordinating organisation / Consortium Leader
- Karolinska Institutet
Cooperation partners with funding
- Karolinska Institutet
- National Veterinary Institute
- University of Giessen
- Uppsala University
