Northwestern University

Apr
24
Mon 2:00 PM

Pyroptosis in Antibacterial Immunity: Sensing and Execution: Feng Shao, PhD

When: Monday, April 24, 2017
2:00 PM - 3:00 PM  

Where: Robert H Lurie Medical Research Center, Baldwin Auditorium, 303 E. Superior, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Dr. Karla Satchell   312.503.2162

Group: Microbiology-Immunology Seminars

Category: Lectures & Meetings

Description:

Microbiology-Immunology Seminar Series

Inflammatory caspases including caspase-1, 4, 5 and 11 are critical for cytosolic defenses against microbial infections. Caspase-1 is activated by canonical inflammasomes that sense diverse bacterial signals or virulence activity; human caspase-4/5 and mouse caspase-11 are cytosolic receptors for bacterial LPS, determining Gram-negative bacteria-induced septic shock. Common to inflammatory caspases activation is pyroptosis, a form of cell death whose nature and mechanism of action were mysterious for more than 20 years. Using genome-wide CRISPR/Cas9 screens, we identify gasdermin D (GSDMD) that is essential for all inflammatory caspases-induced pyroptosis. The caspases cleave GSDMD to release its Gasdermin-N domain for pyroptotic induction. The Gasdermin-N domain binds membrane lipids and exhibits membrane-disrupting cytotoxicity in mammalian cells. Purified Gasdermin-N efficiently lysed the liposomes by forming membrane pores of an inner diameter of 10~14 nm. GSDMD represents a large Gasdermin family (GSDMA-E), many of which are genetically associated with various diseases. While GSDMD is cleaved by inflammatory caspases, other Gasdermins appear to adopt different activation mechanisms and have important functions in other pathophysiological processes. We now redefine pyroptosis as Gasdermin-mediated programmed necrotic cell death.

 

Feng Shao, PhD

Investigator and Deputy Director
National Institute of Biological Sciences, Beijing

Host: Karla Satchell, PhD

 

 

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