NIH VideoCast - Dissecting Regulatory Mechanisms in TLR-Activated Macrophages through Genetic Screening.

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Dissecting Regulatory Mechanisms in TLR-Activated Macrophages through Genetic Screening.

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Air date:	Wednesday, February 17, 2016, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 281 (60 Live, 221 On-demand)
Category:	Immunology
Runtime:	01:02:06
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Immunology Interest Group This week’s IIG speaker will be none other than NIH’s own Iain Fraser. Iain received his Ph.D. in biochemistry from Imperial College, University of London. He was a Wellcome Trust International postdoctoral fellow at the Vollum Institute in Portland, Oregon, following which he joined the Alliance for Cellular Signaling (AfCS) research consortium as lead scientist of the molecular biology group at the California Institute of Technology, rising to co-director of the AfCS Molecular Biology Laboratory. He was recruited to NIAID in 2008 as leader of the PSIIM Molecular and Cell Biology Team, and became Chief of the Signaling Systems Unit (SSU) in the NIAID Laboratory of Systems Biology (LSB) in 2011. Here at NIH Iain has been conducting cutting edge studies using siRNA methods to probe macrophage sensing of pathogens. Combining large-scale screens with modern methods for single cell analysis and computational modeling, he and his colleagues have uncovered a number of novel aspects to PAMP sensing by macrophages, such as a previously unsuspected role for Ikaros in ligand concentration discrimination and major species differences in IRAK function. He has developed many novel reporters for probing macrophage signaling, fostered development of new software tools for analyzing screening data, and made inroads into understanding multi-ligand sensing of intact bacteria by macrophages. He is a member of the international RNAi consortium, served as a member of the IIG steering committee, and is part of the leadership of the Systems Biology Interest Group. Iain is an outstanding speaker and the combination of exciting data on innate immune cell function with his ability to make large-scale data understandable for a broad audience promises to make this a lecture not to be missed. Abstract: Toll-like receptors (TLRs) are a major class of pattern recognition receptors mediating the host response to microbial and inflammatory stimuli. I will describe the use of high-throughput genome-scale technologies (such as siRNA screening and profiling of RNA expression and protein-DNA binding) to broadly characterize the response of innate immune cells to TLR pathway activation. In a comparative screen of canonical TLR pathway genes in human and mouse macrophages, we observe a pattern of conserved signaling module dependencies across species, but with numerous species-specific requirements at the individual gene level. I will further demonstrate how systematic screening and computational analysis can identify important characteristics of innate immune responses across species, dissect distinct innate effector response pathways, and potentially identify specific therapeutic targets for regulating TLR-driven outputs in disease states.

NLM Title:	Dissecting regulatory mechanisms in TLR-Activated macrophages through genetic screening. / Iain Fraser ; Immunology Interest Group.
Author:	Fraser, Iain. National Institutes of Health (U.S.). Immunology Interest Group,
Publisher:
Abstract:	(CIT): This week's IIG speaker will be none other than NIH's own Iain Fraser. Iain received his Ph.D. in biochemistry from Imperial College, University of London. He was a Wellcome Trust International postdoctoral fellow at the Vollum Institute in Portland, Oregon, following which he joined the Alliance for Cellular Signaling (AfCS) research consortium as lead scientist of the molecular biology group at the California Institute of Technology, rising to co-director of the AfCS Molecular Biology Laboratory. He was recruited to NIAID in 2008 as leader of the PSIIM Molecular and Cell Biology Team, and became Chief of the Signaling Systems Unit (SSU) in the NIAID Laboratory of Systems Biology (LSB) in 2011. Here at NIH Iain has been conducting cutting edge studies using siRNA methods to probe macrophage sensing of pathogens. Combining large-scale screens with modern methods for single cell analysis and computational modeling, he and his colleagues have uncovered a number of novel aspects to PAMP sensing by macrophages, such as a previously unsuspected role for Ikaros in ligand concentration discrimination and major species differences in IRAK function. He has developed many novel reporters for probing macrophage signaling, fostered development of new software tools for analyzing screening data, and made inroads into understanding multi-ligand sensing of intact bacteria by macrophages. He is a member of the international RNAi consortium, served as a member of the IIG steering committee, and is part of the leadership of the Systems Biology Interest Group. Iain is an outstanding speaker and the combination of exciting data on innate immune cell function with his ability to make large-scale data understandable for a broad audience promises to make this a lecture not to be missed. Abstract: Toll-like receptors (TLRs) are a major class of pattern recognition receptors mediating the host response to microbial and inflammatory stimuli. I will describe the use of high-throughput genome-scale technologies (such as siRNA screening and profiling of RNA expression and protein-DNA binding) to broadly characterize the response of innate immune cells to TLR pathway activation. In a comparative screen of canonical TLR pathway genes in human and mouse macrophages, we observe a pattern of conserved signaling module dependencies across species, but with numerous species-specific requirements at the individual gene level. I will further demonstrate how systematic screening and computational analysis can identify important characteristics of innate immune responses across species, dissect distinct innate effector response pathways, and potentially identify specific therapeutic targets for regulating TLR-driven outputs in disease states.
Subjects:	Genetic Testing Macrophages--immunology Signal Transduction Toll-Like Receptors--immunology
Publication Types:	Lecture Webcast

NLM Classification:	WH 650
NLM ID:	101678414
CIT Live ID:	18472
Permanent link:	https://videocast.nih.gov/watch=18472

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