Within the special research program for COVID-19 of the Science Fund of the Republic of Serbia, funding was approved for a project Targeting autophagy to combat SARS-CoV2-induced immune dysregulation - TACTICIAN.

The holder of the project is the Faculty of Medicine, University of Belgrade, and the Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade is the participant.

Project website:

https://projecttactician.com/

Leader of the project:

Prof. dr. Vladimir Trajković, Faculty of Medicine, University of Belgrade

Team members from IBISS:

Dr. Maja Misirkić-Marjanović, Department of Neurophysiology IBISS

Dr. Ljubica Harhaji-Trajković, Department of Neurophysiology IBISS

Dr. Ljubica Vučićević, Department of Neurophysiology IBISS

Abstract:

Background: SARS-CoV-2 causes an enhanced inflammatory response that contributes to COVID-19 pathogenesis and severe clinical course in infected patients. Autophagy, a catabolic pathway involved in cell homeostasis, can limit or promote inflammation in a context-dependent manner, but the effects of SARS-CoV-2 on autophagy-immune interplay are unknown.

Novelty: The project will explore for the first time the ability of various SARS-CoV-2 proteins to modulate autophagy-immune interaction in host cells.

Methods: SARS-CoV-2 proteins will be expressed by plasmid vectors in human macrophage, respiratory epithelial, and vascular endhothelial cell lines. Autophagy and its effects on the production of inflammatory mediators will be assessed in target cells stimulated with viral RNA mimics and in sera of COVID-19 patients by confocal/electron microscopy, RT-qPCR, immunoblot, flow cytometry, ELISA, and RNA interference.

Expected results and impact: By revealing how SARS-CoV-2-modulated autophagy affects inflammatory responses, the project will provide grounds for autophagy-based prognosis and therapy of immune dysregulation in COVID-19.