Systems Biology

Giorgi Metreveli, Ph.D.

Influenza A virus is an important human pathogen that causes respiratory disease of different grades of severity according to the specific virus strain and to host susceptibility. Our main hypothesis is that host genes and networks involved in viral replication and in early host responses regulate disease outcome and represent targets for therapeutic intervention. We have assembled interrelated research projects: Project 1 investigates interactions of influenza viruses in vitro. My work focuses on Project 2, which studies the interactions of influenza viruses with host factors and networks in vivo in a mouse model. The aim is to characterize the impact of influenza A virus infection on the mouse lung at the transcriptome, proteome, and metabolome levels, by investigating the early global host responses associated with lethal, severe, and moderate virus infections. We use three clinically relevant strains of influenza A virus that differ in virulence, allowing for comparison of the host responses and interactions associated with different ranges of disease severity.

Here we proposed an OMICS approach to identify key early genes/networks involved in influenza virus pathogenesis. This is achieved by modeling global host responses during influenza virus infection in a mouse model in collaboration with the Modeling Core and the OMICs Cores (Genomics, Proteomics and Metabolomics).

Shashank Tripathi, Ph.D

My work involves development of systems based approaches to study virus-host interactions, specially Influenza A viruses. For this I am using genome wide CRISPR libraries in conjunction with global proteome and transcriptome analysis. I am also investigating broad spectrum cellular innate immune mechanisms against important human viral pathogens such as Influenza, Dengue, Herpes, and HIV. I am also looking at Influenza A virus life cycle events using reporter viruses and live imaging.

Carles Martínez-Romero, Ph.D.

My work is focused on the interactions between the influenza A virus and its various hosts. We recently unveiled the role of two adaptations in the hemagglutinin protein of the pandemic H1N1 influenza A virus that is able to alter viral replication and pathogenicity in a wide variety of in vitro and in vivo models. This provides us with a better insight with regards to the ability of the virus to adapt and go through various reassortments. My research is also focused on the repurposing of current therapeutic compounds in order to find new therapies against the Ebola virus disease. This has led to discovery of several candidates that we are now further testing to confirm newly discovered antiviral properties. Finally, I am currently establishing a collection of primary cells that will serve as novel in vivo platforms for the study of classical and recent influenza viruses, as well as other emerging viruses.

Kris White, Ph.D.

I am interested in understanding and increasing the growth of the influenza B virus component of the influenza vaccine within a proprietary cell line in the generation of a universal influenza vaccine. I have also been working in the “Flu-omics” novel therapeutic target discovery program. In this project we have used a systems biology approach to observe changes in the global host genomic, proteomic and metabolomic response to influenza virus infection. Through models created using these large data sets, we are currently identifying new key cellular proteins and pathways for influenza virus replication, which are potential future targets for therapeutic intervention.

Laser scanning cytometry used to accurately measure influenza infection of a proprietary cell line for novel vaccine production.

Laser scanning cytometry used to accurately measure influenza infection of a proprietary cell line for novel vaccine production.