Objective
Type 1 Diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells, leading to insulin deficiency and severe complications, including cardiovascular disease, neuropathy, and vision impairment. Despite extensive research, the exact cause of T1D remains elusive, and the disease remains incurable. Emerging evidence suggests that β-cells may play an active role in their own demise, alongside the well-documented immune attack. Recent findings have identified protective genes within β-cells that may help them resist immune-mediated destruction.
This project aims to investigate the role of three protective genes—HLA-E, IDO1, and BiP—in preserving β-cell function and survival under autoimmune stress. These genes were identified via a bioinformatic approach that analysed single cell RNA sequencing of β-cells from individuals affected by T1D. The study will begin by modulating the expression of these genes in human EndoC-βH1 cells and human islets, followed by an immune attack model of co-culture with the activated CD8+ T-cells. The goal is to determine which gene(s) offers the most significant protection against β-cell destruction.
Subsequently, the most promising gene(s) will be further evaluated in stem cell-derived β-like cells, which will undergo in vivo testing in immune incompetent NSG mice to mimic more physiologically relevant conditions. The implanted cells will be evaluated by in vivo imaging using an intravital microscopy platform. By silencing or overexpressing these genes, we aim to elucidate the mechanisms that contribute to β-cell resilience, providing insights that could lead to novel therapeutic strategies for enhancing β-cell survival in T1D patients.
This project represents a critical step forward in understanding the interplay between β-cells and the immune system in T1D. It has the potential to uncover new targets for therapy, ultimately improving the quality of life for individuals living with T1D.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciencesclinical medicineendocrinologydiabetes
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesgeneticsRNA
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Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
1050 Bruxelles / Brussel
Belgium