Gasdermin D is a novel effector in the extrinsic apoptosis pathway

Informacje na temat projektu

Inflapoptosis

Identyfikator umowy o grant: 838252

DOI

10.3030/838252

Realizacja projektu zakończyła się 30 Września 2020

Data podpisania przez KE 10 Kwietnia 2019

Data rozpoczęcia 1 Września 2019

Data zakończenia 31 Sierpnia 2021

Finansowanie w ramach

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Koszt całkowity

€ 191 149,44

Wkład UE

€ 191 149,44

Koordynowany przez

UNIVERSITE DE LAUSANNE
Switzerland

Periodic Reporting for period 1 - Inflapoptosis (Gasdermin D is a novel effector in the extrinsic apoptosis pathway)

Okres sprawozdawczy: 2019-09-01 do 2021-08-31

Podsumowanie kontekstu i ogólnych celów projektu

Gasdermin D (GSDMD) is a recently described pore-forming protein that is important for host defence against infection. However, emerging studies also implicate GSDMD in a variety of inflammatory diseases through poorly characterised mechanisms.
The aim of this study is to investigate the molecular and cellular mechanisms by which GSDMD promote inflammatory disease, so that better drug candidates can be identified in future. Here, we characterised the molecular mechanisms by which GSDMD promotes
tumour necrosis factor(TNF)-driven diseases. We show that caspase-8-dependent GSDMD activation promotes TNF-driven disease in mice. Our study thus uncovers novel drug targets for TNF-driven diseases.

Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty

-Generation of caspase-3-uncleavable GSDMD mouse model
-Demonstration that caspase-3-uncleavable GSDMD mouse do not suffer from auto-inflammatory disease
-Validated that GSDMD activation promotes anti-microbial defence
-Validated that GSDMD activation promotes TNF-driven lethality

Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)

TNF-mediated diseases were traditionally believed to be solely driven by necroptosis, a form of necrotic death. Multi labs and biotech companies are developing such inhibitors to block these pathways, however, there are limited success.
Our work has now uncovered GSDMD, as a novel player in TNF-driven disease, therefore providing a new drug target.

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