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Nuclear magnetic resonance spectroscopy of liquid-liquid phase separation

Objective

Liquid-liquid phase separation (LLPS) is a phenomenon inherent to the thermodynamics of liquids, is critical for the development of technologically useful fluids and underlies some of the biggest health changes in our society. LLPS is based on transitions between two different forms of liquid that have the same chemical composition, but distinct energy, entropy and density. Despite the importance of LLPS for technology and health, however, only a very low-resolution view primarily through light microscopy is currently available for LLPS states formed by peptides and proteins. Because of this bottleneck, the interactions, which stabilize liquid droplets, and regulate their biogenesis, as well as a rationale for the biochemical function of LLPS, have remained mysterious.

To tackle this massive unmet need, I propose to develop powerful methods of NMR spectroscopy that go far beyond the state-of-the-art and team them up with mechanobiology/force microscopy to break the resolution barrier of polypeptide LLPS and push the description of the internal organization of liquid droplets from micrometer to sub-nanometer. Although highly challenging, the novel methods when successful will (i) disentangle the structure and kinetics of intrinsically disordered proteins within LLPS reaction chambers in space and time, (ii) unravel the nature of chemical reactions in liquid droplets, and (iii) decipher LLPS regulation by posttranslational modifications, nucleic acids and critical changes in cellular environment at atomic resolution. The innovative nature of the proposal is designed to unravel the innermost forces in liquid droplets and to transform our knowledge about the chemistry of liquid phase-separated protein states. Findings from this proposal will provide critical guidance in the development of systems to encapsulate bioactive molecules and to develop better treatments for human diseases.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2017-ADG

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Host institution

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
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.

€ 2 460 278,00
Address
VENUSBERG-CAMPUS 1/99
53127 Bonn
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 460 278,00

Beneficiaries (1)

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