A common theme in human diseases is a central role for inflammation and its appropriate regulation. Inflammation, defined as a response to pathogenic or host stimuli that results in tissue damage and repair, can lead to pathological outcomes when the host response is not controlled appropriately. Innate immune cells, such as macrophages, play a critical role in almost all inflammatory diseases, and recently established ‘big data’ technologies now allow the analysis of immune responses and host-pathogen interactions at a global level, across scales ranging from intracellular signaling networks to individual cell behaviour to the functioning of a tissue, an organ, and the whole organism. The challenge is not only to collect the large amounts of data such methods permit, but also to organize the information in a manner that enhances our understanding of how the immune system operates or how pathogens affect their hosts.

My research program is focused on the design, implementation, and interpretation of screening efforts to identify and determine the interactions among components of innate immune signaling networks activated by pattern recognition receptors (PRRs). We use high-throughput genetic screening to identify key pathway regulators, and a combination of cell biology, biochemistry, and molecular biology to characterize their function. Our goal is to obtain a better understanding of how PRR signaling pathways control the macrophage inflammatory state, and ultimately to develop strategies to regulate these responses in human inflammatory diseases. I will describe ongoing projects from our group that are addressing this challenge.

Fraser Bio:

Iain Fraser is Chief of the Signaling Systems Section and a Senior Investigator in the Laboratory of Immune System Biology at the National Institute of Allergy and Infectious Disease at NIH. He received his undergraduate degree in biochemistry from Heriot-Watt University, Edinburgh, UK and his Ph.D. in Biochemistry from Imperial College, University of London, UK. He was a Wellcome Trust International Prize postdoctoral fellow at the Vollum Institute, Oregon, USA before joining the Alliance for Cellular Signaling (AfCS) research consortium at the California Institute of Technology (Caltech). He led the AfCS Molecular Biology Laboratory at Caltech before joining NIAID in 2008. His research focuses on the mechanistic basis of cellular signaling, particularly in the context of regulation of inflammatory responses in cells of the innate immune system. His lab uses systems biology approaches to decipher how macrophages respond to pathogenic and host stimuli through pattern recognition receptors to ensure appropriate context-dependent cellular responses.