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Protein-RNA phase-separated condensates and their capacity for catalysis (PhaseCat)

Objective

The debate of how life has evolved and which biomolecules (DNA, RNA and/or proteins) came first is still ongoing. What is clear is that
RNA and proteins must have closely co-evolved, considering their essential interactions in the cell e.g. in the ribosome, an ancient
protein-RNA complex indispensable for protein production in all cells. The ribosome catalyses two key reactions: aminolysis, where
peptide bonds are formed, and peptidyl hydrolysis, where the complete protein is released after translation. Both reactions occur at
the peptidyl-transferase centre, the active site composed of RNA. On the other hand, an enormous variety of reactions are catalysed
by the enzymatic activity of peptides and proteins. Given their evolutionary co-occurrence, it is likely that the catalytic capabilities of
proteins and RNA originally co-evolved. Importantly, proteins and RNA can form phase-separated condensates (PSCs), membraneless
organelles that perform key functions in present-day cells. As PSCs form spontaneously, this raises the possibility that they were
functional in the primordial soup as well. This idea is especially compelling because PSCs can, due to increased molecular
concentrations, enhance catalytic capacity. In PhaseCat, we address how such protein-RNA catalytic reactions may have evolved in
PSCs, especially in the context of primordial translation, and how they could be exploited for industrially relevant reactions. The
combination of fundamental and applied research forms an ideal training ground for doctoral students, who will be trained to
understand protein-RNA interactions leading to phase separation, a central biological mechanism with exploitation potential.
PhaseCat integrates high-throughput screening of PSCs through microfluidics combined with Raman spectroscopy, analysis of
biological catalysis by proteins/RNA and its application in green chemistry, and computational methods to tie together all
components, predict properties and inform experiment.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-DN - HORIZON TMA MSCA Doctoral Networks

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Call for proposal

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(opens in new window) HORIZON-MSCA-2025-DN-01

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Coordinator

VRIJE UNIVERSITEIT BRUSSEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 865 620,00
Address
PLEINLAAN 2
1050 Bruxelles / Brussel
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Participants (4)

Partners (2)