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How to design a kill switch: Lessons from the AIM2-ASC inflammasome

Event Details

Event Dates: 

Wednesday, April 18, 2018 - 3:30pm

Seminar Location: 

  • JSCBB Butcher Auditorium

Speaker Name(s): 

Jungsan Sohn
Seminar Type/Subject

Scientific Seminar Type: 

  • Biochemistry Seminar

Event Details & Abstract: 

TheAIM2-ASC inflammasome is a filamentous signaling platform essential for hostdefense against cytoplasmic dsDNA, with its primary role being inducingcell-death. We show here that longer dsDNA is more effective in inducing AIM2assembly, its self-propagation, and downstream ASC polymerization. Thisobservation is related to the increased probability of forming the base of AIM2filaments, and indicates that the assembly discerns small dsDNA as noise ateach signaling step. Filaments assembled by receptor AIM2, downstream ASC, andtheir joint complex all persist regardless of dsDNA, consequently generatingsustained signal amplification and hysteresis. Furthermore, multiple positivefeedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate theassembly of nascent AIM2 with or without dsDNA. Together with a quantitativemodel of the assembly, our results indicate that an ultrasensitive digitalcircuit drives the assembly of the AIM2-ASC inflammasome.