Viral pathogenesis of type 1 diabetes - novel mechanisms and biomarker discovery

Understatedly, the underlying mechanisms of the viral pathogenesis of type 1 diabetes (T1D) are far from fully understood.

Hence, the purpose of this project is to identify novel mechanisms and pathways underlying this enigma and to discover surrogate biomarkers for β-cell infection.

To achieve our goal, we propose to perform in-depth investigations into the effects of enterovirus infection on the regulation of β-cell autophagy and its interplay with the secretion of extracellular vesicles (EVs). Our overall aim is to delineate how the viral dysregulation of these pathways can lead to β-cell decay.

Specifically, we will investigate i) if enterovirus infection triggers changes in the autophagic transcriptome, and determine how this in turn influences β-cell function, ii) if enterovirus infection modifies the β-cell EV proteome and miRNAome, iii) if autophagy-driven EVs mediate non-lytic viral spread and infection of β-cells, iv) if EVs secreted from enterovirus-infected β-cells can activate dendritic cells and "fan the flames" of β-cell autoimmunity, and v) if circulating EVs could be used as biomarkers for viral infection in β-cells.

We will employ cutting-edge technologies, state-of-the-art methods, and an integrative multi-omics systems biology approach.

Should viral dysregulation of EV–autophagy networks prove to be a fundamental pathogenic mechanism in T1D, therapeutics targeting these pathways have the potential to halt T1D.