Summary
Cellular behaviour is methodically studied using systems biology approaches that analyse the presence, absence, or oscillation of biomolecules. To this end, exogenous perturbations, among others, are used to alter protein expression and study their effects on cellular homeostasis. However, proteomes are inherently versatile and diversified by alternative splicing, protein cleavage, and post-translational modifications (PTM). Similarly, the spatiotemporal formation of multicomponent complexes plays an important but less well understood role in cellular homoeostasis and disorders. Specific recognition of these complexes by ligands is a difficult task to solve. Therefore, deciphering signalling cascades at the proteome and complex levels requires technologies that enable the identification of protein-binding and -inhibiting compounds that are sensitive or tolerant to PTMs and can recognize protein complexes. Intracellularly expressed aptamers, known as intramers, offer a solution to this challenge. The IntraMAP project will develop generally applicable paradigms for the automated evolution of intramers and combine them with cellular screening methods. In this way, intramers will be identified that are optimally adapted to cellular environments and effectively disrupt signalling cascades. These intramers will be used to identify signalling components and protein complexes associated with these cascades. They will be applied to various cells, organoids and in vivo to uncover fundamental principles of complex signalling events. The project has a strong interdisciplinary focus and will open novel avenues for the analysis of biomolecules. It has implications ranging from life sciences to systems biology, and will not only establish intramers as a broadly applicable discovery technology to study signalling cascades on an ‘omics’-like scale, but also holds enormous innovative potential for the development of novel gene therapies and future RNA-based drugs.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101140898 |
| Start date: | 01-10-2024 |
| End date: | 30-09-2029 |
| Total budget - Public funding: | 2 499 241,00 Euro - 2 499 241,00 Euro |
Cordis data
Original description
Cellular behaviour is methodically studied using systems biology approaches that analyse the presence, absence, or oscillation of biomolecules. To this end, exogenous perturbations, among others, are used to alter protein expression and study their effects on cellular homeostasis. However, proteomes are inherently versatile and diversified by alternative splicing, protein cleavage, and post-translational modifications (PTM). Similarly, the spatiotemporal formation of multicomponent complexes plays an important but less well understood role in cellular homoeostasis and disorders. Specific recognition of these complexes by ligands is a difficult task to solve. Therefore, deciphering signalling cascades at the proteome and complex levels requires technologies that enable the identification of protein-binding and -inhibiting compounds that are sensitive or tolerant to PTMs and can recognize protein complexes. Intracellularly expressed aptamers, known as intramers, offer a solution to this challenge. The IntraMAP project will develop generally applicable paradigms for the automated evolution of intramers and combine them with cellular screening methods. In this way, intramers will be identified that are optimally adapted to cellular environments and effectively disrupt signalling cascades. These intramers will be used to identify signalling components and protein complexes associated with these cascades. They will be applied to various cells, organoids and in vivo to uncover fundamental principles of complex signalling events. The project has a strong interdisciplinary focus and will open novel avenues for the analysis of biomolecules. It has implications ranging from life sciences to systems biology, and will not only establish intramers as a broadly applicable discovery technology to study signalling cascades on an ‘omics’-like scale, but also holds enormous innovative potential for the development of novel gene therapies and future RNA-based drugs.Status
SIGNEDCall topic
ERC-2023-ADGUpdate Date
21-11-2024
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