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Order and Disorder at the Surface of Biological Membranes.

Project description

Elucidating protein interactions and structural disorder at the membrane surface

Macromolecular interactions at biological membranes play a central role in various processes including cellular signalling, the assembly of molecular machinery and the regulation of vesicular trafficking. However, the transient nature and the dynamics of these interactions pose a technological challenge to their analysis. The EU-funded BioDisOrder project is in the process of developing a novel tool that combines nuclear magnetic resonance (NMR) spectroscopy and molecular simulations. This tool has the potential to determine the structure, dynamics and kinetics of complex protein–protein and protein–membrane interactions at the membrane surface, including processes that involve disordered systems that are untreatable with current methodologies. Using these tools, researchers will study the complexity of the neuronal synapse and address key questions in neuroscience.

Objective

Heterogeneous biomolecular mechanisms at the surface of cellular membranes are often fundamental to generate function and dysfunction in living systems. These processes are governed by transient and dynamical macromolecular interactions that pose tremendous challenges to current analytical tools, as the majority of these methods perform best in the study of well-defined and poorly dynamical systems. This proposal aims at a radical innovation in the characterisation of complex processes that are dominated by structural order and disorder, including those occurring at the surface of biological membranes such as cellular signalling, the assembly of molecular machinery, or the regulation vesicular trafficking.
I outline a programme to realise a vision where the combination of experiments and theory can delineate a new analytical platform to study complex biochemical mechanisms at a multiscale level, and to elucidate their role in physiological and pathological contexts. To achieve this ambitious goal, my research team will develop tools based on the combination of nuclear magnetic resonance (NMR) spectroscopy and molecular simulations, which will enable probing the structure, dynamics, thermodynamics and kinetics of complex protein-protein and protein-membrane interactions occurring at the surface of cellular membranes. The ability to advance both the experimental and theoretical sides, and their combination, is fundamental to define the next generation of methods to achieve our transformative aims. We will provide evidence of the innovative nature of the proposed multiscale approach by addressing some of the great questions in neuroscience and elucidate the details of how functional and aberrant biological complexity is achieved via the fine tuning between structural order and disorder at the neuronal synapse.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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-COG - Consolidator 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-2018-COG

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Host institution

UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
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.

€ 1 983 664,64
Address
CORSO UMBERTO I, 40
80138 Napoli
Italy

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Region
Sud Campania Napoli
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 983 664,64

Beneficiaries (2)

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