Innate DNA sensing through the cGAS-STING system - Blurring the boundary between PAMP and DAMP
Event details
| Date | 17.12.2018 |
| Hour | 12:15 › 13:15 |
| Speaker | Dr Andrea Ablasser |
| Location | |
| Category | Conferences - Seminars |
Abstract :
The life of any organism depends on the ability of cells to accurately recognize and eliminate harmful microbes. In order to detect the immense repertoire of pathogenic entities, the innate immune system of mammals has evolved a range of distinct sensing strategies. One major mechanism is based on the recognition of microbial DNA - an invariant and highly immunogenic pathogen-associated molecular pattern (PAMP). Host cells, however, contain abundant sources of self-DNA. In the context of cellular damage or metabolic derangement, “out-of-the-context” self-DNA can elicit potentially damaging inflammatory responses, thus serving as a potent danger-associated molecular pattern (DAMP).
In my laboratory at EPFL, we study primarily the so-called cGAS-STING system - an evolutionary highly conserved innate DNA sensing system. On DNA binding, cGAS is activated to produce a second messenger cyclic dinucleotide (cyclic GMP-AMP), which stimulates the adaptor protein STING to induce innate immune responses. While this process was originally discovered as a crucial component of immune defense against pathogens, recent work has elucidated a pathogenic role for innate DNA sensing in a variety of sterile inflammatory diseases. In this seminar I will give an overview of our contributions to the understanding of the molecular mechanisms underlying innate DNA recognition and highlight how such knowledge may be leveraged to develop innovative new medicines.
Selected References:
Haag et al., Nature 2018 Jul;559(7713):269-273.
Gulen et al., Nature Communications 2017 Sep 5;8(1):427.
Glück et al., Nature Cell Biology 2017 Sep;19(9):1061-1070.
Wassermann et al., Cell Host & Microbe 2015 Jun 10;17(6):799-810.
Ablasser* et al., Nature 2013 Jun 20;498(7454):380-4.
The life of any organism depends on the ability of cells to accurately recognize and eliminate harmful microbes. In order to detect the immense repertoire of pathogenic entities, the innate immune system of mammals has evolved a range of distinct sensing strategies. One major mechanism is based on the recognition of microbial DNA - an invariant and highly immunogenic pathogen-associated molecular pattern (PAMP). Host cells, however, contain abundant sources of self-DNA. In the context of cellular damage or metabolic derangement, “out-of-the-context” self-DNA can elicit potentially damaging inflammatory responses, thus serving as a potent danger-associated molecular pattern (DAMP).
In my laboratory at EPFL, we study primarily the so-called cGAS-STING system - an evolutionary highly conserved innate DNA sensing system. On DNA binding, cGAS is activated to produce a second messenger cyclic dinucleotide (cyclic GMP-AMP), which stimulates the adaptor protein STING to induce innate immune responses. While this process was originally discovered as a crucial component of immune defense against pathogens, recent work has elucidated a pathogenic role for innate DNA sensing in a variety of sterile inflammatory diseases. In this seminar I will give an overview of our contributions to the understanding of the molecular mechanisms underlying innate DNA recognition and highlight how such knowledge may be leveraged to develop innovative new medicines.
Selected References:
Haag et al., Nature 2018 Jul;559(7713):269-273.
Gulen et al., Nature Communications 2017 Sep 5;8(1):427.
Glück et al., Nature Cell Biology 2017 Sep;19(9):1061-1070.
Wassermann et al., Cell Host & Microbe 2015 Jun 10;17(6):799-810.
Ablasser* et al., Nature 2013 Jun 20;498(7454):380-4.
Practical information
- General public
- Free
Organizer
- SV Faculty / M. Mary, H. Hirling
Contact
- M. Mary