ProMisMe
Financiado
Bioengineered microbes as a platform for discovering chemical rescuers of diseas...
Bioengineered microbes as a platform for discovering chemical rescuers of disease-related misfolding of integral membrane proteins
Protein misfolding diseases (PMDs) are a large group of human disorders caused by the misfolding of specific proteins. They include conditions with high socio-economic impact, such as Alzheimer’s disease, cystic fibrosis, obesity...
Protein misfolding diseases (PMDs) are a large group of human disorders caused by the misfolding of specific proteins. They include conditions with high socio-economic impact, such as Alzheimer’s disease, cystic fibrosis, obesity and type 2 diabetes, and the majority of them remain incurable. Among the >70 PMDs, about 1/3 are caused by misfolding-prone membrane proteins (MisMPs). Despite their significance, and mainly due to the difficulties associated with MisMP overexpression, isolation and characterization, the PMD scientific community has largely overlooked MisMP-associated PMDs, thus limiting opportunities for drug discovery. In ProMisMe, we will develop engineered bacteria and yeast, which can function as broadly applicable discovery platforms for compounds that rescue MisMP misfolding. These compounds will be selected from libraries of drug-like molecules biosynthesized in these microbes using a technology that allows the facile production of tens of millions to tens of billions of different test molecules. These libraries will then be screened in the same microbial cells that produce them and the rare molecules that rescue MisMP misfolding effectively will be selected by ultrahigh-throughput screening. The effect of the selected molecules on MisMP folding will then evaluated by biochemical and biophysical methods, while their ability to reverse MisMP-induced pathogenicity will be tested in appropriate mammalian cell assays. The molecules that rescue the misfolding and associated pathogenicity of the target MisMPs will become therapeutic candidates against the corresponding diseases. This procedure will be applied for different MisMPs to identify potential therapeutics for two serious PMDs: Usher Syndrome III and Charcot-Marie-Tooth disease. Successful realization of ProMisMe will provide invaluable therapeutic leads against major diseases and a more widely applicable framework for drug discovery against diseases caused by membrane protein misfolding.
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Duración del proyecto: 32 meses
Fecha Inicio: 2023-10-19
Fecha Fin: 2026-06-30
Fecha Fin: 2026-06-30
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-10-19
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
Presupuesto
El presupuesto total del proyecto asciende a
212K€
Líder del proyecto
EREVNITIKO KENTRO VIOIATRIKON EPISTIMON ALEXA...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5