Using RNAi to discover genes and networks of the immune system

06/09/2010 13:30
America/New York
Speaker: Nir Hacohen,
Assistant Professor, Harvard Medical School.

Venue: TAC Auditorium
1 Gilbert st.
New Haven, CT

Abstract
The recent development of systematic measurement and perturbation technologies in mammalian cells should enable the reconstruction of molecular networks with some mechanistic detail. I will describe two biological systems that we have utilized for this purpose. In the first system of primary mouse dendritic cells stimulated with pathogen-derived components (such as LPS), we used validated RNAi constructs to perturb candidate regulators of this response, and multiplex transcript detection technology to monitor network output. This led us to identify indirect and direct targets of transcription and chromatin factors that are active during an innate immune response to pathogens. In the second system of primary human lung epithelial cells infected with influenza virus, we experimentally uncovered the physical influenza-host cell interactions and the stereotyped transcriptional responses of cells to influenza infection. To develop a functional model of the virus-host relationship, we used RNAi to test the roles of genes identified (with these two approaches) in protection from viral infection.