Graduate Student Colby Hladun in the Chemistry and Biochemistry Department here at Clarkson University will present about Non-canoncical dsDNA structure, Guanosine Quadruplex modulates cGAS- STING activation: The sensing of foreign and self-cytosolic DNA is a crucial role of innate immunity regulated by cytosolic DNA sensing pathways such as the cGAS-STING pathway. cGAS intitiates innate immune signalling in the presence of cytosolic double stranded DNA (dsDNA) equal to or greater than 18 base pairs in length. The recognition of dsDNA catalyzes the production of the cyclic-dinucleotide secondary messenger, 2’,3’ cGAMP to initiate innate immune response through the activation of STING and subsequent activation of type I interferons. Understanding the underlying mechanisms of cGAS activation and it’s ability to recognize DNA and modulate STING activation is crucial for further development of treatments for autoimmune disorders. Here, we demonstrate that the activation of cGAS may be modulated by the presence of non-canonical secondary dsDNA structure guanosine-quadruplex (G4) in an inhibitory manner. Where, cGAS activation can be modulated in a dose dependent manner with G4 stabilizers such as Pyridostain, BRACO-19, and PIPER. We leverage these results for a potential treatment of lysosomal storage disorder, Niemann Pick Disease Type C’s (NPC) autoimmune response by induction of G4 in NPC dependent accumulated cytosolic DNA.
Friday, September 13th, 2024, 3:30 PM, BH Snell Hall 214Potsdam Campus
Zoom Information: Link
Meeting ID: 950 1099 7564
Passcode: chemistry